7-117616239-T-TC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000492.4(CFTR):​c.3468+1526_3468+1527insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 151,844 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 33)
Failed GnomAD Quality Control

Consequence

CFTR
NM_000492.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFTRNM_000492.4 linkc.3468+1526_3468+1527insC intron_variant Intron 21 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.3468+1526_3468+1527insC intron_variant Intron 21 of 26 1 NM_000492.4 ENSP00000003084.6 P13569-1

Frequencies

GnomAD3 genomes
AF:
0.00469
AC:
711
AN:
151726
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000944
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00243
Gnomad ASJ
AF:
0.00433
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000624
Gnomad FIN
AF:
0.00747
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00774
Gnomad OTH
AF:
0.00479
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.00468
AC:
711
AN:
151844
Hom.:
1
Cov.:
33
AF XY:
0.00471
AC XY:
350
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.000941
Gnomad4 AMR
AF:
0.00243
Gnomad4 ASJ
AF:
0.00433
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000624
Gnomad4 FIN
AF:
0.00747
Gnomad4 NFE
AF:
0.00774
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00261
Hom.:
0
Bravo
AF:
0.00382
Asia WGS
AF:
0.000869
AC:
3
AN:
3468

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: rs148384591; hg19: chr7-117256293; API