rs4148712

Positions:

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

Variant summary

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

The NM_000492.4(CFTR):​c.2619+86_2619+87del 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

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 7-117595142-CAT-C is Benign according to our data. Variant chr7-117595142-CAT-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
CFTR	NM_000492.4	c.2619+86_2619+87del		intron_variant		ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.2619+86_2619+87del		intron_variant		1	NM_000492.4	ENSP00000003084	P2

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

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.339

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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.381

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

Benign, criteria provided, single submitter

curation

CFTR-France

Jan 09, 2018

the variant does not result in CFTR-RD neither -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs4148712; hg19: chr7-117235196;