11-2847638-G-A

Variant names:

• chr11-2847638-G-A
• rs79788804
• NM_000218.3:c.1795-129G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):​c.1795-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 843,118 control chromosomes in the GnomAD database, including 3,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (491 hom., cov: 33)
  • Exomes 𝑓: 0.073 (2639 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0680
• Publications: 2 publications found

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-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-2847638-G-A is Benign according to our data. Variant chr11-2847638-G-A is described in ClinVar as [Benign]. Clinvar id is 1231618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-129G>A		intron_variant	Intron 15 of 15	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1795-129G>A		intron_variant	Intron 15 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9931 AN: 152146 Hom.: 491 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0685

GnomAD4 exome AF: 0.0734 AC: 50724 AN: 690854 Hom.: 2639 AF XY: 0.0731 AC XY: 26424 AN XY: 361486

African (AFR) AF: 0.0207 AC: 379 AN: 18306

American (AMR) AF: 0.224 AC: 7322 AN: 32746

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 988 AN: 19210

East Asian (EAS) AF: 0.0541 AC: 1761 AN: 32562

South Asian (SAS) AF: 0.0855 AC: 5236 AN: 61264

European-Finnish (FIN) AF: 0.113 AC: 3982 AN: 35334

Middle Eastern (MID) AF: 0.0538 AC: 165 AN: 3066

European-Non Finnish (NFE) AF: 0.0631 AC: 28621 AN: 453528

Other (OTH) AF: 0.0652 AC: 2270 AN: 34838

GnomAD4 genome AF: 0.0653 AC: 9940 AN: 152264 Hom.: 491 Cov.: 33 AF XY: 0.0692 AC XY: 5148 AN XY: 74432

African (AFR) AF: 0.0236 AC: 979 AN: 41560

American (AMR) AF: 0.139 AC: 2130 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3470

East Asian (EAS) AF: 0.0564 AC: 292 AN: 5174

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4830

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4413 AN: 68014

Other (OTH) AF: 0.0668 AC: 141 AN: 2110

Alfa AF: 0.0633 Hom.: 630

Bravo AF: 0.0664

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.87
PhyloP100		0.068
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79788804; hg19: chr11-2868868; COSMIC: COSV50140486;