7-117548606-ATGTGTGTG-ATGTGTG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000492.4(CFTR):c.1210-13_1210-12delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,335,714 control chromosomes in the GnomAD database, including 17,978 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.26 ( 5655 hom., cov: 0)

Exomes 𝑓: 0.20 ( 12323 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0750

Publications

2 publications found

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 -16 ACMG points.

BP6

Variant 7-117548606-ATG-A is Benign according to our data. Variant chr7-117548606-ATG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 439475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.1210-13_1210-12delGT		intron_variant	Intron 9 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1 link	n.222-6069_222-6068delCA		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.1210-34_1210-33delTG		intron_variant	Intron 9 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

36639

AN:

143230

Hom.:

5641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.00103

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.222

AC:

39472

AN:

177682

AF XY:

0.225

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0237

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.205

AC:

244096

AN:

1192382

Hom.:

12323

AF XY:

0.204

AC XY:

120680

AN XY:

591510

show subpopulations

African (AFR)

AF:

0.422

AC:

13019

AN:

30818

American (AMR)

AF:

0.147

AC:

5570

AN:

37880

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

2866

AN:

19082

East Asian (EAS)

AF:

0.0186

AC:

621

AN:

33366

South Asian (SAS)

AF:

0.149

AC:

10378

AN:

69468

European-Finnish (FIN)

AF:

0.250

AC:

11099

AN:

44428

Middle Eastern (MID)

AF:

0.219

AC:

1034

AN:

4722

European-Non Finnish (NFE)

AF:

0.210

AC:

189421

AN:

903470

Other (OTH)

AF:

0.205

AC:

10088

AN:

49148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9790

19581

29371

39162

48952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6654

13308

19962

26616

33270

<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:

0.256

AC:

36691

AN:

143332

Hom.:

5655

Cov.:

AF XY:

0.252

AC XY:

17562

AN XY:

69656

show subpopulations

African (AFR)

AF:

0.459

AC:

18035

AN:

39292

American (AMR)

AF:

0.193

AC:

2809

AN:

14530

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

338

AN:

3286

East Asian (EAS)

AF:

0.00103

AC:

AN:

4846

South Asian (SAS)

AF:

0.108

AC:

478

AN:

4438

European-Finnish (FIN)

AF:

0.250

AC:

2303

AN:

9194

Middle Eastern (MID)

AF:

0.202

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.187

AC:

12108

AN:

64694

Other (OTH)

AF:

0.233

AC:

462

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1196

2393

3589

4786

5982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.171

Hom.:

240

Bravo

AF:

0.251

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 17, 2018

GeneDx

Significance:Benign

Review Status:flagged submission

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Apr 29, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1210-14_1210-13delTG in intron 9 of CFTR: This variant is not expected to have clinical significance because it has been identified in 47% (582/3375) of Afric an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs3832534).

Cystic fibrosis

Benign:2

Jan 29, 2018

CFTR-France

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

the variant does not result in CFTR-RD neither

Dec 17, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 27, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Oct 11, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Other strong data

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.075

La Branchor

0.64

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over