rs800337

Positions:

• chr11-2452081-T-C

Variant summary

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

The NM_000218.3(KCNQ1):​c.386+6597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,142 control chromosomes in the GnomAD database, including 44,897 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 0.76 (44897 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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 = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.386+6597T>C		intron_variant		ENST00000155840.12
KCNQ1	NM_001406836.1	c.386+6597T>C		intron_variant
KCNQ1	NM_001406837.1	c.24+6597T>C		intron_variant
KCNQ1	NM_001406838.1	c.386+6597T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+6597T>C		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000345015.4	n.163+6597T>C		intron_variant, non_coding_transcript_variant		1
KCNQ1	ENST00000496887.7	c.125+6597T>C		intron_variant		5
KCNQ1	ENST00000646564.2	c.386+6597T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115965 AN: 152024 Hom.: 44874 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.763 AC: 116037 AN: 152142 Hom.: 44897 Cov.: 33 AF XY: 0.759 AC XY: 56455 AN XY: 74378

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.772

Alfa AF: 0.791 Hom.: 8846

Bravo AF: 0.753

Asia WGS AF: 0.585 AC: 2034 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	0.077
DANN	Benign	0.40

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: rs800337; hg19: chr11-2473311;