rs10229820

Positions:

chr7-117548628-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000492.4(CFTR):c.1210-13G>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

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:):

CFTR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CFTR	NM_000492.4 linkuse as main transcript	c.1210-13G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000003084.11
CFTR-AS1	NR_149084.1 linkuse as main transcript	n.222-6089C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11 linkuse as main transcript	c.1210-13G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000492.4	P2	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

GnomAD3 exomes

AF:

0.0713

AC:

14618

AN:

205052

Hom.:

539

AF XY:

0.0718

AC XY:

8032

AN XY:

111880

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 SAS exome

AF:

0.0494

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

Gnomad4 AMR exome

AF:

0.0414

Gnomad4 ASJ exome

AF:

0.0846

Gnomad4 EAS exome

AF:

0.00727

Gnomad4 SAS exome

AF:

0.0551

Gnomad4 FIN exome

AF:

0.0918

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.0787

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

Gnomad4 AMR

AF:

0.0799

Gnomad4 ASJ

AF:

0.0831

Gnomad4 EAS

AF:

0.00769

Gnomad4 SAS

AF:

0.0539

Gnomad4 FIN

AF:

0.0838

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.0380

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 28, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2014	- -

CFTR-related disorder

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Dec 29, 2021	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). -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

Cystic fibrosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2021

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2018

Other strong data -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

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

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 02, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.031

DANN

Benign

0.23

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