7-117599568-ATT-A

Variant names:

• chr7-117599568-ATT-A
• rs138816759
• NM_000492.4:c.2620-3257_2620-3256delTT

Variant summary

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

The NM_000492.4(CFTR):​c.2620-3257_2620-3256delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 152,218 control chromosomes in the GnomAD database, including 38 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (38 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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 = 0.0145 (2200/152218) while in subpopulation AFR AF= 0.0325 (1352/41566). AF 95% confidence interval is 0.0311. There are 38 homozygotes in gnomad4. There are 1095 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.2620-3257_2620-3256delTT		intron_variant	Intron 15 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.2620-3257_2620-3256delTT		intron_variant	Intron 15 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2192 AN: 152100 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00608

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0145 AC: 2200 AN: 152218 Hom.: 38 Cov.: 32 AF XY: 0.0147 AC XY: 1095 AN XY: 74426

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.00608

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.0142

Asia WGS AF: 0.0230 AC: 80 AN: 3466

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: rs138816759; hg19: chr7-117239622;