7-117611845-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_000492.4(CFTR):c.3367+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,476,608 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 15 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0880

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 Gene-Disease associations (from GenCC):

cystic fibrosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
congenital bilateral absence of vas deferens
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary chronic pancreatitis
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CFTR links:

ENSG00000083622 (HGNC:):

ENSG00000083622 links:

CFTR-AS2 (HGNC:40145):

CFTR-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-117611845-G-A is Benign according to our data. Variant chr7-117611845-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 439073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.3367+37G>A		intron_variant	Intron 20 of 26	ENST00000003084.11	NP_000483.3	P13569-1A0A024R730
CFTR-AS2	NR_199597.1 link	n.177+4384C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.3367+37G>A		intron_variant	Intron 20 of 26	1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

335

AN:

151430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00389

Gnomad OTH

AF:

0.00193

GnomAD2 exomes

AF:

0.00216

AC:

484

AN:

224434

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.000994

Gnomad ASJ exome

AF:

0.000518

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00200

Gnomad NFE exome

AF:

0.00365

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.00338

AC:

4478

AN:

1325062

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

2186

AN XY:

665428

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

30618

American (AMR)

AF:

0.00112

AC:

AN:

42944

Ashkenazi Jewish (ASJ)

AF:

0.000436

AC:

AN:

25208

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38636

South Asian (SAS)

AF:

0.00155

AC:

128

AN:

82424

European-Finnish (FIN)

AF:

0.00201

AC:

100

AN:

49718

Middle Eastern (MID)

AF:

0.00110

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00401

AC:

3983

AN:

994248

Other (OTH)

AF:

0.00340

AC:

190

AN:

55814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

216

431

647

862

1078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00221

AC:

335

AN:

151546

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

144

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.000629

AC:

AN:

41318

American (AMR)

AF:

0.00105

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00188

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00389

AC:

264

AN:

67884

Other (OTH)

AF:

0.00191

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00204

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 13, 2019

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 27, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cystic fibrosis

Benign:1

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.85

(source)

DANN

Benign

0.28

PhyloP100

-0.088

PromoterAI

0.0036

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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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7-117611845-G-A

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