chr7-117499429-C-CTGTGTG

Variant names:

• chr7-117499429-C-CTGTGTG
• rs56985019
• NM_000492.4:c.54-4796_54-4791dupGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000492.4(CFTR):​c.54-4796_54-4791dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2022 hom., cov: 0)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.54-4796_54-4791dupGTGTGT		intron_variant	Intron 1 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.54-4824_54-4823insTGTGTG		intron_variant	Intron 1 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.163 AC: 22126 AN: 135666 Hom.: 2019 Cov.: 0

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0993

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 22141 AN: 135762 Hom.: 2022 Cov.: 0 AF XY: 0.167 AC XY: 10818 AN XY: 64970

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56985019; hg19: chr7-117139483;