7-117499429-CTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr7-117499429-C-CTGTGTGTGTGTGTG
• rs56985019
• NM_000492.4:c.54-4804_54-4791dupGTGTGTGTGTGTGT

Variant summary

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

The NM_000492.4(CFTR):​c.54-4804_54-4791dupGTGTGTGTGTGTGT 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 0.067 (554 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 = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.54-4804_54-4791dupGTGTGTGTGTGTGT		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_54-4823insTGTGTGTGTGTGTG		intron_variant	Intron 1 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 9118 AN: 135676 Hom.: 555 Cov.: 0

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0240

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0430

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0628

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

GnomAD4 genome AF: 0.0672 AC: 9122 AN: 135774 Hom.: 554 Cov.: 0 AF XY: 0.0654 AC XY: 4251 AN XY: 65000

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0240

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0158

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0622

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;