rs4148711

Positions:

• chr7-117590591-T-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFTR	NM_000492.4	c.1766+152T>A		intron_variant		ENST00000003084.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFTR	ENST00000003084.11	c.1766+152T>A		intron_variant		1	NM_000492.4	P2

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

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.327

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

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.379

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

Benign, criteria provided, single submitter

curation

CFTR-France

Jan 29, 2018

the variant does not result in CFTR-RD neither -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.44

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: rs4148711; hg19: chr7-117230645;