rs739677

chr11-2452750-G-Achr11-2452750-G-T

Variant summary

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

The NM_000218.3(KCNQ1):c.386+7266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,148 control chromosomes in the GnomAD database, including 28,164 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 0.56 (28164 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.386+7266G>A		intron_variant		ENST00000155840.12
KCNQ1	NM_001406836.1	c.386+7266G>A		intron_variant
KCNQ1	NM_001406837.1	c.24+7266G>A		intron_variant
KCNQ1	NM_001406838.1	c.386+7266G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+7266G>A		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000345015.4	n.163+7266G>A		intron_variant, non_coding_transcript_variant		1
KCNQ1	ENST00000496887.7	c.125+7266G>A		intron_variant		5
KCNQ1	ENST00000646564.2	c.386+7266G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84753 AN: 152030 Hom.: 28166 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.557 AC: 84745 AN: 152148 Hom.: 28164 Cov.: 33 AF XY: 0.557 AC XY: 41453 AN XY: 74378

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.582

Alfa AF: 0.661 Hom.: 16841

Bravo AF: 0.532

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.091
Dann	Benign	0.67

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: rs739677; hg19: chr11-2473980;