chr11-2631427-T-G

Position:

• chr11-2631427-T-G

Variant summary

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

The NM_000218.3(KCNQ1):​c.1394-30534T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 390,536 control chromosomes in the GnomAD database, including 24,240 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 0.32 (8648 hom., cov: 32)
  • Exomes 𝑓: 0.35 (15592 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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]

KCNQ1OT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1394-30534T>G		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1394-30534T>G		intron_variant		1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 48576 AN: 149904 Hom.: 8638 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.346 AC: 83218 AN: 240524 Hom.: 15592 Cov.: 0 AF XY: 0.345 AC XY: 42073 AN XY: 121780

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.324 AC: 48617 AN: 150012 Hom.: 8648 Cov.: 32 AF XY: 0.337 AC XY: 24690 AN XY: 73254

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.332

Alfa AF: 0.193 Hom.: 450

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.38

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: rs10832417; hg19: chr11-2652657;