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. The variant received 0 ACMG points: 0P and 0B.

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AC: 0 AN: 0

Gnomad4 NFE exome AC: 0 AN: 0

Gnomad4 Remaining exome AC: 0 AN: 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 AC: 0.000941211 AN: 0.000941211

Gnomad4 AMR AF: 0.00243 AC: 0.00243005 AN: 0.00243005

Gnomad4 ASJ AF: 0.00433 AC: 0.00432526 AN: 0.00432526

Gnomad4 EAS AF: 0.000193 AC: 0.000193424 AN: 0.000193424

Gnomad4 SAS AF: 0.000624 AC: 0.00062422 AN: 0.00062422

Gnomad4 FIN AF: 0.00747 AC: 0.00747257 AN: 0.00747257

Gnomad4 NFE AF: 0.00774 AC: 0.00773743 AN: 0.00773743

Gnomad4 OTH AF: 0.00474 AC: 0.00474383 AN: 0.00474383

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;