Variant 11-2445305-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000218.3(KCNQ1):c.207G>A(p.Ala69Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A69A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

KCNQ1
NM_000218.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16

Variant links:

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]

KCNQ1 links:

KCNQ1 (HGNC:):

KCNQ1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-2445305-G-A is Benign according to our data. Variant chr11-2445305-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1595379.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3 linkuse as main transcript	c.207G>A	p.Ala69Ala	synonymous_variant	1/16	ENST00000155840.12	NP_000209.2	P51787-1Q96AI9
KCNQ1	NM_001406836.1 linkuse as main transcript	c.207G>A	p.Ala69Ala	synonymous_variant	1/15		NP_001393765.1
KCNQ1	NM_001406838.1 linkuse as main transcript	c.207G>A	p.Ala69Ala	synonymous_variant	1/11		NP_001393767.1
KCNQ1	NM_001406837.1 linkuse as main transcript	c.-156G>A		5_prime_UTR_variant	1/17		NP_001393766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNQ1	ENST00000155840.12 linkuse as main transcript	c.207G>A	p.Ala69Ala	synonymous_variant	1/16	1	NM_000218.3	ENSP00000155840.2	P51787-1
KCNQ1	ENST00000646564.2 linkuse as main transcript	c.207G>A	p.Ala69Ala	synonymous_variant	1/11			ENSP00000495806.2	A0A2R8YEQ9
KCNQ1	ENST00000496887.7 linkuse as main transcript	c.24-78G>A		intron_variant		5		ENSP00000434560.2	E9PPZ0
KCNQ1	ENST00000345015.4 linkuse as main transcript	n.-17G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

97640

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

56448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000167

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000310

AC:

AN:

1288626

Hom.:

Cov.:

AF XY:

0.00000315

AC XY:

AN XY:

635354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000369

Gnomad4 AMR exome

AF:

0.0000400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.68e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.0000727

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.6

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over