7-117616239-T-TC

Variant names:

• chr7-117616239-T-TC
• rs148384591
• NM_000492.4:c.3468+1526_3468+1527insC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000492.4(CFTR):​c.3468+1526_3468+1527insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 151,844 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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]

ENSG00000083622 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.3468+1526_3468+1527insC		intron_variant	Intron 21 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.3468+1526_3468+1527insC		intron_variant	Intron 21 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.00469 AC: 711 AN: 151726 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00243

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00747

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00774

Gnomad OTH AF: 0.00479

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00468 AC: 711 AN: 151844 Hom.: 1 Cov.: 33 AF XY: 0.00471 AC XY: 350 AN XY: 74232

Gnomad4 AFR AF: 0.000941

Gnomad4 AMR AF: 0.00243

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00747

Gnomad4 NFE AF: 0.00774

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00382

Asia WGS AF: 0.000869 AC: 3 AN: 3468

ClinVar

Not reported in ClinVar

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: rs148384591; hg19: chr7-117256293;