NM_000492.4:c.54-4798_54-4791dupGTGTGTGT

Variant names:

• chr7-117499429-C-CTGTGTGTG
• rs56985019
• NM_000492.4:c.54-4798_54-4791dupGTGTGTGT

Variant summary

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

The NM_000492.4(CFTR):​c.54-4798_54-4791dupGTGTGTGT 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 0.025 (90 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 (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.54-4798_54-4791dupGTGTGTGT		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_54-4823insTGTGTGTG		intron_variant	Intron 1 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3354 AN: 135784 Hom.: 88 Cov.: 0

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00706

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.00523

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.00592

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0265

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0248 AC: 3374 AN: 135880 Hom.: 90 Cov.: 0 AF XY: 0.0248 AC XY: 1611 AN XY: 65044

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.00523

Gnomad4 EAS AF: 0.0163

Gnomad4 SAS AF: 0.00568

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0226

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;