7-117536514-AGATT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000492.4(CFTR):c.744-9_744-6del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,535,716 control chromosomes in the GnomAD database, including 38,096 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4348 hom., cov: 25)
  • Exomes 𝑓: 0.21 (33748 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.82

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-117536514-AGATT-A is Benign according to our data. Variant chr7-117536514-AGATT-A is described in ClinVar as [Benign]. Clinvar id is 43579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign]. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFTR	NM_000492.4	c.744-9_744-6del		intron_variant		ENST00000003084.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11	c.744-9_744-6del		intron_variant		1	NM_000492.4	P2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35190 AN: 151540 Hom.: 4333 Cov.: 25

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.270 AC: 44068 AN: 163440 Hom.: 6756 AF XY: 0.267 AC XY: 23220 AN XY: 86906

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.415

Gnomad SAS exome AF: 0.345

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.212 AC: 292985 AN: 1384058 Hom.: 33748 AF XY: 0.215 AC XY: 147376 AN XY: 684806

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.232 AC: 35245 AN: 151658 Hom.: 4348 Cov.: 25 AF XY: 0.242 AC XY: 17941 AN XY: 74088

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.225

Bravo AF: 0.232

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 20, 2011	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	Ambry Genetics	Nov 19, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

CFTR-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

May 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1805171; hg19: chr7-117176568;