11-2796565-C-T

Position:

• chr11-2796565-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.1794+18528C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,210 control chromosomes in the GnomAD database, including 6,571 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 0.29 (6571 hom., cov: 34)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

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]

LOC124902614 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) 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.1794+18528C>T		intron_variant		ENST00000155840.12	NP_000209.2
LOC124902614	XR_007062554.1	n.1271+1810G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1794+18528C>T		intron_variant		1	NM_000218.3	ENSP00000155840	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 44020 AN: 152090 Hom.: 6564 Cov.: 34

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.289 AC: 44057 AN: 152210 Hom.: 6571 Cov.: 34 AF XY: 0.282 AC XY: 20994 AN XY: 74424

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.302

Alfa AF: 0.292 Hom.: 1294

Bravo AF: 0.296

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.84

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: rs234881; hg19: chr11-2817795;