chr11-2818521-C-T

Position:

• chr11-2818521-C-T

Variant summary

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

The NM_000218.3(KCNQ1):​c.1795-29246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 152,156 control chromosomes in the GnomAD database, including 1,189 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 0.096 (1189 hom., cov: 32)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-29246C>T		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1795-29246C>T		intron_variant		1	NM_000218.3	ENSP00000155840	P1

Frequencies

GnomAD3 genomes AF: 0.0958 AC: 14571 AN: 152038 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.0960 AC: 14612 AN: 152156 Hom.: 1189 Cov.: 32 AF XY: 0.0975 AC XY: 7254 AN XY: 74396

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0556

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0739 Hom.: 1567

Bravo AF: 0.111

Asia WGS AF: 0.198 AC: 685 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	1.8
DANN	Benign	0.40

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: rs2237892; hg19: chr11-2839751;