rs179406

Variant names:

• chr11-2504971-A-C
• rs179406
• NM_000218.3:c.387-22957A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2504971-A-C
• chr11-2504971-A-G
• chr11-2504971-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000218.3(KCNQ1):​c.387-22957A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,978 control chromosomes in the GnomAD database, including 37,083 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 0.69 (37083 hom., cov: 31)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.387-22957A>C		intron_variant	Intron 1 of 15	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.387-22957A>C		intron_variant	Intron 1 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104863 AN: 151860 Hom.: 37079 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.690 AC: 104902 AN: 151978 Hom.: 37083 Cov.: 31 AF XY: 0.689 AC XY: 51147 AN XY: 74266

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.720

Alfa AF: 0.727 Hom.: 10513

Bravo AF: 0.680

Asia WGS AF: 0.727 AC: 2522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.16

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: rs179406; hg19: chr11-2526201;