7-117563520-GA-G

Variant names:

• chr7-117563520-GA-G
• rs4148707
• NM_000492.4:c.1584+3867delA

Variant summary

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

The NM_000492.4(CFTR):​c.1584+3867delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 151,922 control chromosomes in the GnomAD database, including 139 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.037 (139 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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]

CFTR-AS1 (HGNC:40144): (CFTR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0372 (5650/151922) while in subpopulation AFR AF= 0.0455 (1885/41438). AF 95% confidence interval is 0.0438. There are 139 homozygotes in gnomad4. There are 3013 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 139 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1584+3867delA		intron_variant	Intron 11 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1	n.161+995delT		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1584+3866delA		intron_variant	Intron 11 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5639 AN: 151804 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0372 AC: 5650 AN: 151922 Hom.: 139 Cov.: 32 AF XY: 0.0406 AC XY: 3013 AN XY: 74244

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0314

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0345 Hom.: 17

Bravo AF: 0.0294

Asia WGS AF: 0.0340 AC: 118 AN: 3478

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: rs4148707; hg19: chr7-117203574;