7-117523153-GA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000492.4(CFTR):​c.274-7743delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,214 control chromosomes in the GnomAD database, including 73 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 73 hom., cov: 32)

Consequence

CFTR
NM_000492.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0199 (3027/152214) while in subpopulation NFE AF= 0.0218 (1480/68018). AF 95% confidence interval is 0.0208. There are 73 homozygotes in gnomad4. There are 1783 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFTRNM_000492.4 linkc.274-7743delA intron_variant Intron 3 of 26 ENST00000003084.11 NP_000483.3 P13569-1A0A024R730

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFTRENST00000003084.11 linkc.274-7745delA intron_variant Intron 3 of 26 1 NM_000492.4 ENSP00000003084.6 P13569-1

Frequencies

GnomAD3 genomes
AF:
0.0198
AC:
3018
AN:
152096
Hom.:
71
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00391
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.00681
Gnomad ASJ
AF:
0.00691
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.114
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0218
Gnomad OTH
AF:
0.00908
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0199
AC:
3027
AN:
152214
Hom.:
73
Cov.:
32
AF XY:
0.0240
AC XY:
1783
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.00390
Gnomad4 AMR
AF:
0.00680
Gnomad4 ASJ
AF:
0.00691
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.114
Gnomad4 NFE
AF:
0.0218
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0218
Hom.:
6
Bravo
AF:
0.0109
Asia WGS
AF:
0.0120
AC:
40
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201153822; hg19: chr7-117163207; API