rs800336

Positions:

• chr11-2451901-G-A

Variant summary

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

The NM_000218.3(KCNQ1):​c.386+6417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,098 control chromosomes in the GnomAD database, including 28,321 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 0.56 (28321 hom., cov: 32)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.386+6417G>A		intron_variant		ENST00000155840.12
KCNQ1	NM_001406836.1	c.386+6417G>A		intron_variant
KCNQ1	NM_001406837.1	c.24+6417G>A		intron_variant
KCNQ1	NM_001406838.1	c.386+6417G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+6417G>A		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000345015.4	n.163+6417G>A		intron_variant, non_coding_transcript_variant		1
KCNQ1	ENST00000496887.7	c.125+6417G>A		intron_variant		5
KCNQ1	ENST00000646564.2	c.386+6417G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84509 AN: 151980 Hom.: 28324 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.556 AC: 84499 AN: 152098 Hom.: 28321 Cov.: 32 AF XY: 0.556 AC XY: 41369 AN XY: 74352

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.579

Alfa AF: 0.701 Hom.: 66575

Bravo AF: 0.530

Asia WGS AF: 0.483 AC: 1679 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	5.3
DANN	Benign	0.66

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: rs800336; hg19: chr11-2473131;