GeneBe

rs774046442

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000218.3(KCNQ1):​c.1902C>A​(p.Gly634Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G634G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KCNQ1
NM_000218.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

0 publications found
Variant links:
Genes affected
KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]
KCNQ1-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP7
Synonymous conserved (PhyloP=-1.11 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNQ1NM_000218.3 linkc.1902C>A p.Gly634Gly synonymous_variant Exon 16 of 16 ENST00000155840.12 NP_000209.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNQ1ENST00000155840.12 linkc.1902C>A p.Gly634Gly synonymous_variant Exon 16 of 16 1 NM_000218.3 ENSP00000155840.2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
190130
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1426522
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
706442
African (AFR)
AF:
0.00
AC:
0
AN:
32698
American (AMR)
AF:
0.00
AC:
0
AN:
40554
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25436
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37622
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81658
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49348
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1094512
Other (OTH)
AF:
0.00
AC:
0
AN:
58974
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.080
DANN
Benign
0.55
PhyloP100
-1.1

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

Other links and lift over

dbSNP: rs774046442; hg19: chr11-2869104; API