chr7-117499429-C-CTGTG

Variant names:

• chr7-117499429-C-CTGTG
• rs56985019
• NM_000492.4:c.54-4794_54-4791dupGTGT

Variant summary

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

The NM_000492.4(CFTR):​c.54-4794_54-4791dupGTGT 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 0.038 (155 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 (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.54-4794_54-4791dupGTGT		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_54-4823insTGTG		intron_variant	Intron 1 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5133 AN: 135712 Hom.: 156 Cov.: 0

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00588

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0194

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0397

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0338

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

GnomAD4 genome AF: 0.0379 AC: 5149 AN: 135808 Hom.: 155 Cov.: 0 AF XY: 0.0432 AC XY: 2807 AN XY: 65014

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0194

Gnomad4 EAS AF: 0.0220

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.0351

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;