7-117590591-T-A

Variant names:

• chr7-117590591-T-A
• rs4148711
• NM_000492.4:c.1766+152T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.1766+152T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 955,520 control chromosomes in the GnomAD database, including 61,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15691 hom., cov: 31)
  • Exomes 𝑓: 0.32 (45700 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0350
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-117590591-T-A is Benign according to our data. Variant chr7-117590591-T-A is described in ClinVar as Benign. ClinVar VariationId is 818094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000492.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1766+152T>A		intron	N/A	NP_000483.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1766+152T>A		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1766+152T>A		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1676+152T>A		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65304 AN: 151722 Hom.: 15653 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.319 AC: 256633 AN: 803680 Hom.: 45700 AF XY: 0.320 AC XY: 128462 AN XY: 401418

African (AFR) AF: 0.653 AC: 12124 AN: 18558

American (AMR) AF: 0.434 AC: 7784 AN: 17926

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 2539 AN: 14782

East Asian (EAS) AF: 0.398 AC: 11948 AN: 30034

South Asian (SAS) AF: 0.393 AC: 20884 AN: 53134

European-Finnish (FIN) AF: 0.405 AC: 10002 AN: 24724

Middle Eastern (MID) AF: 0.261 AC: 645 AN: 2472

European-Non Finnish (NFE) AF: 0.295 AC: 178989 AN: 606214

Other (OTH) AF: 0.327 AC: 11718 AN: 35836

GnomAD4 genome AF: 0.431 AC: 65390 AN: 151840 Hom.: 15691 Cov.: 31 AF XY: 0.434 AC XY: 32203 AN XY: 74216

African (AFR) AF: 0.647 AC: 26823 AN: 41476

American (AMR) AF: 0.420 AC: 6406 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2155 AN: 5150

South Asian (SAS) AF: 0.418 AC: 2016 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4526 AN: 10534

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21780 AN: 67816

Other (OTH) AF: 0.379 AC: 798 AN: 2108

Alfa AF: 0.394 Hom.: 1855

Bravo AF: 0.439

Asia WGS AF: 0.468 AC: 1628 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

not provided Benign:1

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.44
PhyloP100		-0.035
Mutation Taster		=88/12	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148711; hg19: chr7-117230645;