rs2283228

Positions:

• chr11-2828300-A-C
• chr11-2828300-A-G

Variant summary

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

The NM_000218.3(KCNQ1):​c.1795-19467A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,284 control chromosomes in the GnomAD database, including 1,365 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 0.11 (1365 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-19467A>C		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1795-19467A>C		intron_variant		1	NM_000218.3	ENSP00000155840	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16100 AN: 152166 Hom.: 1357 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.106 AC: 16129 AN: 152284 Hom.: 1365 Cov.: 33 AF XY: 0.107 AC XY: 7990 AN XY: 74456

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0865 Hom.: 845

Bravo AF: 0.122

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78

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: rs2283228; hg19: chr11-2849530;