7-117583314-TC-T

Variant names:

• chr7-117583314-TC-T
• rs368344796
• NM_000492.4:c.1585-4416delC

Variant summary

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

The NM_000492.4(CFTR):​c.1585-4416delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 149,272 control chromosomes in the GnomAD database, including 51 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.017 (51 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 (AMR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1585-4416delC		intron_variant	Intron 11 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1585-4424delC		intron_variant	Intron 11 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2481 AN: 149174 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.00404

Gnomad FIN AF: 0.000393

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000552

Gnomad OTH AF: 0.0142

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

GnomAD4 genome AF: 0.0168 AC: 2513 AN: 149272 Hom.: 51 Cov.: 32 AF XY: 0.0174 AC XY: 1271 AN XY: 72892

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.00404

Gnomad4 FIN AF: 0.000393

Gnomad4 NFE AF: 0.000552

Gnomad4 OTH AF: 0.0136

Alfa AF: 0.0000639 Hom.: 0

Bravo AF: 0.0231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs368344796; hg19: chr7-117223368;