Variant 7-117610711-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000492.4(CFTR):c.3139+42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,604,986 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 228 hom., cov: 31)

Exomes 𝑓: 0.0095 ( 272 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.171

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:

ENSG00000083622 (HGNC:):

ENSG00000083622 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=-0.83).

BP6

Variant 7-117610711-A-T is Benign according to our data. Variant chr7-117610711-A-T is described in ClinVar as [Benign]. Clinvar id is 619836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFTR	NM_000492.4 linkuse as main transcript	c.3139+42A>T		intron_variant		ENST00000003084.11	NP_000483.3	P13569-1A0A024R730

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 linkuse as main transcript	c.3139+42A>T		intron_variant		1	NM_000492.4	ENSP00000003084.6		P13569-1

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

5151

AN:

152176

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0153

AC:

3777

AN:

247534

Hom.:

107

AF XY:

0.0145

AC XY:

1935

AN XY:

133800

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00370

Gnomad EAS exome

AF:

0.00215

Gnomad SAS exome

AF:

0.0275

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00926

GnomAD4 exome

AF:

0.00951

AC:

13812

AN:

1452692

Hom.:

272

Cov.:

AF XY:

0.00975

AC XY:

7048

AN XY:

722960

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00712

Gnomad4 ASJ exome

AF:

0.00296

Gnomad4 EAS exome

AF:

0.00292

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00546

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0340

AC:

5185

AN:

152294

Hom.:

228

Cov.:

AF XY:

0.0336

AC XY:

2503

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0238

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.0362

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 18, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cystic fibrosis

Benign:2

Benign, criteria provided, single submitter	curation	CFTR-France	Jan 29, 2018	the variant does not result in CFTR-RD neither -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.65

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