11-2789501-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000218.3(KCNQ1):​c.1794+11464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,270 control chromosomes in the GnomAD database, including 763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.094 ( 763 hom., cov: 33)

Consequence

KCNQ1
NM_000218.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.91
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNQ1NM_000218.3 linkc.1794+11464C>T intron_variant Intron 15 of 15 ENST00000155840.12 NP_000209.2 P51787-1Q96AI9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNQ1ENST00000155840.12 linkc.1794+11464C>T intron_variant Intron 15 of 15 1 NM_000218.3 ENSP00000155840.2 P51787-1

Frequencies

GnomAD3 genomes
AF:
0.0945
AC:
14383
AN:
152152
Hom.:
762
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0778
Gnomad AMI
AF:
0.0209
Gnomad AMR
AF:
0.0998
Gnomad ASJ
AF:
0.0533
Gnomad EAS
AF:
0.194
Gnomad SAS
AF:
0.107
Gnomad FIN
AF:
0.0904
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0993
Gnomad OTH
AF:
0.0851
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0945
AC:
14389
AN:
152270
Hom.:
763
Cov.:
33
AF XY:
0.0967
AC XY:
7201
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0778
Gnomad4 AMR
AF:
0.0998
Gnomad4 ASJ
AF:
0.0533
Gnomad4 EAS
AF:
0.193
Gnomad4 SAS
AF:
0.108
Gnomad4 FIN
AF:
0.0904
Gnomad4 NFE
AF:
0.0993
Gnomad4 OTH
AF:
0.0851
Alfa
AF:
0.0969
Hom.:
1737
Bravo
AF:
0.0933
Asia WGS
AF:
0.132
AC:
458
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.010
DANN
Benign
0.72

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: rs2237886; hg19: chr11-2810731; API