NM_000492.4:c.54-4806_54-4791dupGTGTGTGTGTGTGTGT

Variant names:

• chr7-117499429-C-CTGTGTGTGTGTGTGTG
• rs56985019
• NM_000492.4:c.54-4806_54-4791dupGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000492.4(CFTR):​c.54-4806_54-4791dupGTGTGTGTGTGTGTGT 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 0.018 (55 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0183 (2480/135888) while in subpopulation AFR AF= 0.0455 (1597/35066). AF 95% confidence interval is 0.0437. There are 55 homozygotes in gnomad4. There are 1119 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.54-4806_54-4791dupGTGTGTGTGTGTGTGT		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_54-4823insTGTGTGTGTGTGTGTG		intron_variant	Intron 1 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2472 AN: 135790 Hom.: 55 Cov.: 0

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00215

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00123

Gnomad FIN AF: 0.00260

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00943

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0183 AC: 2480 AN: 135888 Hom.: 55 Cov.: 0 AF XY: 0.0172 AC XY: 1119 AN XY: 65054

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.00215

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00123

Gnomad4 FIN AF: 0.00260

Gnomad4 NFE AF: 0.00943

Gnomad4 OTH AF: 0.0124

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;