rs757092

Positions:

• chr11-2477948-G-A
• chr11-2477948-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000218.3(KCNQ1):​c.386+32464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,952 control chromosomes in the GnomAD database, including 22,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22351 hom., cov: 31)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-2477948-G-A is Benign according to our data. Variant chr11-2477948-G-A is described in ClinVar as [Benign]. Clinvar id is 1600312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.386+32464G>A		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+32464G>A		intron_variant		1	NM_000218.3	ENSP00000155840	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78924 AN: 151834 Hom.: 22335 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.520 AC: 78982 AN: 151952 Hom.: 22351 Cov.: 31 AF XY: 0.520 AC XY: 38646 AN XY: 74268

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.552

Alfa AF: 0.553 Hom.: 4552

Bravo AF: 0.500

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.52

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: rs757092; hg19: chr11-2499178;