7-117504756-TAAAAAAAA-TAAAAAAAAA

Variant names:

• chr7-117504756-T-TA
• rs372341779
• NM_000492.4:c.164+410dupA

Variant summary

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

The NM_000492.4(CFTR):​c.164+410dupA 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 0.14 (3377 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.164+410dupA		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+394insA		intron_variant	Intron 2 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.142 AC: 17178 AN: 121038 Hom.: 3375 Cov.: 0

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.00132

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0489

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.00314

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.142 AC: 17192 AN: 121020 Hom.: 3377 Cov.: 0 AF XY: 0.139 AC XY: 7958 AN XY: 57334

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.0589

Gnomad4 ASJ AF: 0.0489

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.00314

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.130

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: rs372341779; hg19: chr7-117144810;