rs4148712

Variant names:

• chr7-117595142-CAT-C
• rs4148712
• NM_000492.4:c.2619+86_2619+87delTA

Your query was ambiguous. Multiple possible variants found:

• chr7-117595142-CAT-C
• chr7-117595142-CAT-CATAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.2619+86_2619+87delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,065,238 control chromosomes in the GnomAD database, including 72,004 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16071 hom., cov: 0)
  • Exomes 𝑓: 0.33 (55933 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.181
• Publications: 4 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 -16 ACMG points.

• BP6: Variant 7-117595142-CAT-C is Benign according to our data. Variant chr7-117595142-CAT-C is described in ClinVar as Benign. ClinVar VariationId is 818087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.2619+86_2619+87delTA		intron_variant	Intron 15 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.2619+85_2619+86delAT		intron_variant	Intron 15 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65757 AN: 151218 Hom.: 16033 Cov.: 0

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.334 AC: 305105 AN: 913908 Hom.: 55933 AF XY: 0.334 AC XY: 159081 AN XY: 476352

African (AFR) AF: 0.672 AC: 14990 AN: 22316

American (AMR) AF: 0.454 AC: 18857 AN: 41498

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 3888 AN: 22278

East Asian (EAS) AF: 0.403 AC: 14580 AN: 36162

South Asian (SAS) AF: 0.395 AC: 28741 AN: 72812

European-Finnish (FIN) AF: 0.411 AC: 20192 AN: 49152

Middle Eastern (MID) AF: 0.263 AC: 800 AN: 3044

European-Non Finnish (NFE) AF: 0.302 AC: 188954 AN: 625100

Other (OTH) AF: 0.339 AC: 14103 AN: 41546

GnomAD4 genome AF: 0.435 AC: 65840 AN: 151330 Hom.: 16071 Cov.: 0 AF XY: 0.438 AC XY: 32364 AN XY: 73902

African (AFR) AF: 0.665 AC: 27423 AN: 41258

American (AMR) AF: 0.421 AC: 6405 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2139 AN: 5134

South Asian (SAS) AF: 0.417 AC: 2008 AN: 4810

European-Finnish (FIN) AF: 0.428 AC: 4452 AN: 10390

Middle Eastern (MID) AF: 0.248 AC: 71 AN: 286

European-Non Finnish (NFE) AF: 0.321 AC: 21728 AN: 67774

Other (OTH) AF: 0.381 AC: 799 AN: 2098

Alfa AF: 0.409 Hom.: 1751

Bravo AF: 0.443

Asia WGS AF: 0.465 AC: 1608 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystic fibrosis Benign:1

Jan 09, 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

Jul 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=100/0	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: rs4148712; hg19: chr7-117235196;