chr7-117504756-T-TAAA

Variant names:

• chr7-117504756-T-TAAA
• rs372341779
• NM_000492.4:c.164+408_164+410dupAAA

Variant summary

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

The NM_000492.4(CFTR):​c.164+408_164+410dupAAA 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 0.020 (32 hom., cov: 0)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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 = 0.0197 (2388/121040) while in subpopulation AFR AF= 0.0242 (839/34618). AF 95% confidence interval is 0.0229. There are 32 homozygotes in gnomad4. There are 1064 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.164+408_164+410dupAAA		intron_variant	Intron 2 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.164+393_164+394insAAA		intron_variant	Intron 2 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2390 AN: 121058 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0437

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00280

Gnomad FIN AF: 0.00662

Gnomad MID AF: 0.0317

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0180

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

GnomAD4 genome AF: 0.0197 AC: 2388 AN: 121040 Hom.: 32 Cov.: 0 AF XY: 0.0186 AC XY: 1064 AN XY: 57340

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00253

Gnomad4 FIN AF: 0.00662

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0180

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: rs372341779; hg19: chr7-117144810;