chr7-117548628-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000492.4(CFTR):c.1210-13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,542,054 control chromosomes in the GnomAD database, including 4,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 610 hom., cov: 30)

Exomes 𝑓: 0.078 ( 3879 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.455

Variant links:

Genes affected

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR links:

CFTR-AS1 (HGNC:40144): (CFTR antisense RNA 1)

CFTR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-117548628-G-T is Benign according to our data. Variant chr7-117548628-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 162962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117548628-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.1210-13G>T		intron_variant	Intron 9 of 26	ENST00000003084.11	NP_000483.3	P13569-1A0A024R730
CFTR-AS1	NR_149084.1 link	n.222-6089C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.1210-13G>T		intron_variant	Intron 9 of 26	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

13483

AN:

142324

Hom.:

609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.0494

Gnomad AMR

AF:

0.0800

Gnomad ASJ

AF:

0.0831

Gnomad EAS

AF:

0.00806

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.0838

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0713

AC:

14618

AN:

205052

AF XY:

0.0718

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.0828

Gnomad EAS exome

AF:

0.00522

Gnomad FIN exome

AF:

0.0896

Gnomad NFE exome

AF:

0.0856

Gnomad OTH exome

AF:

0.0804

GnomAD4 exome

AF:

0.0779

AC:

109019

AN:

1399628

Hom.:

3879

Cov.:

AF XY:

0.0778

AC XY:

54166

AN XY:

696312

show subpopulations

Gnomad4 AFR exome

AF:

0.122

AC:

3736

AN:

30598

Gnomad4 AMR exome

AF:

0.0414

AC:

1743

AN:

42052

Gnomad4 ASJ exome

AF:

0.0846

AC:

2042

AN:

24130

Gnomad4 EAS exome

AF:

0.00727

AC:

279

AN:

38362

Gnomad4 SAS exome

AF:

0.0551

AC:

4567

AN:

82876

Gnomad4 FIN exome

AF:

0.0918

AC:

4717

AN:

51356

Gnomad4 NFE exome

AF:

0.0814

AC:

86848

AN:

1067374

Gnomad4 Remaining exome

AF:

0.0787

AC:

4516

AN:

57364

Heterozygous variant carriers

5659

11318

16977

22636

28295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

3248

6496

9744

12992

16240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0947

AC:

13494

AN:

142426

Hom.:

610

Cov.:

AF XY:

0.0935

AC XY:

6491

AN XY:

69442

show subpopulations

Gnomad4 AFR

AF:

0.131

AC:

0.130853

AN:

0.130853

Gnomad4 AMR

AF:

0.0799

AC:

0.0799026

AN:

0.0799026

Gnomad4 ASJ

AF:

0.0831

AC:

0.0830887

AN:

0.0830887

Gnomad4 EAS

AF:

0.00769

AC:

0.00768624

AN:

0.00768624

Gnomad4 SAS

AF:

0.0539

AC:

0.0538698

AN:

0.0538698

Gnomad4 FIN

AF:

0.0838

AC:

0.0837653

AN:

0.0837653

Gnomad4 NFE

AF:

0.0896

AC:

0.0895678

AN:

0.0895678

Gnomad4 OTH

AF:

0.108

AC:

0.108452

AN:

0.108452

Heterozygous variant carriers

516

1032

1549

2065

2581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0380

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Feb 28, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 31, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

CFTR-related disorder

Benign:3

May 10, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 29, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cystic fibrosis

Benign:1

Dec 18, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Oct 09, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Other strong data -

Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1

Benign:1

Feb 02, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.031

DANN

Benign

0.23

Mutation Taster

=11/89

disease causing (long InDel)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over