rs2283205

Positions:

• chr11-2720097-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.1515-48747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,214 control chromosomes in the GnomAD database, including 2,500 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 0.18 (2500 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1515-48747C>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.1515-48747C>T		intron_variant		1	NM_000218.3	ENSP00000155840	P1
KCNQ1	ENST00000335475.6	c.1134-48747C>T		intron_variant		1		ENSP00000334497
KCNQ1	ENST00000496887.7	c.1158-48747C>T		intron_variant		5		ENSP00000434560
KCNQ1	ENST00000646564.2	c.975-48747C>T		intron_variant				ENSP00000495806

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26868 AN: 152096 Hom.: 2497 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.177 AC: 26882 AN: 152214 Hom.: 2500 Cov.: 33 AF XY: 0.172 AC XY: 12803 AN XY: 74442

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.174

Alfa AF: 0.176 Hom.: 2318

Bravo AF: 0.179

Asia WGS AF: 0.173 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.54

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: rs2283205; hg19: chr11-2741327;