Variant chr7-117548606-A-ATGTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The ENST00000003084.11(CFTR):c.1210-15_1210-12dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00087 ( 0 hom. )

Consequence

CFTR
ENST00000003084.11 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0650

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 -8 ACMG points.

BP6

Variant 7-117548606-A-ATGTG is Benign according to our data. Variant chr7-117548606-A-ATGTG is described in ClinVar as [Benign]. Clinvar id is 496577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFTR	NM_000492.4 linkuse as main transcript	c.1210-15_1210-12dup		intron_variant		ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1 linkuse as main transcript	n.222-6068_222-6067insCACA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 linkuse as main transcript	c.1210-15_1210-12dup		intron_variant		1	NM_000492.4	ENSP00000003084	P2	P13569-1

Frequencies

GnomAD3 genomes

AF:

0.000927

AC:

133

AN:

143504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00243

AC:

431

AN:

177682

Hom.:

AF XY:

0.00244

AC XY:

233

AN XY:

95626

show subpopulations

Gnomad AFR exome

AF:

0.000438

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.000156

Gnomad EAS exome

AF:

0.0209

Gnomad SAS exome

AF:

0.00279

Gnomad FIN exome

AF:

0.000121

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.000461

GnomAD4 exome

AF:

0.000866

AC:

1186

AN:

1370286

Hom.:

Cov.:

AF XY:

0.000878

AC XY:

598

AN XY:

681206

show subpopulations

Gnomad4 AFR exome

AF:

0.000663

Gnomad4 AMR exome

AF:

0.000874

Gnomad4 ASJ exome

AF:

0.0000832

Gnomad4 EAS exome

AF:

0.0115

Gnomad4 SAS exome

AF:

0.00244

Gnomad4 FIN exome

AF:

0.0000403

Gnomad4 NFE exome

AF:

0.000426

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000912

AC:

131

AN:

143604

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

AN XY:

69794

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.000216

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystic fibrosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2021	- -
Benign, criteria provided, single submitter	curation	CFTR-France	Jan 29, 2018	the variant does not result in CFTR-RD neither -

CFTR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

La Branchor

0.64

BranchPoint Hunter

2.0

Splicing

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