chr11-2450312-A-G

Position:

• chr11-2450312-A-G

Variant summary

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

The NM_000218.3(KCNQ1):​c.386+4828A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,058 control chromosomes in the GnomAD database, including 8,729 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 0.29 (8729 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.386+4828A>G		intron_variant		ENST00000155840.12	NP_000209.2
KCNQ1	NM_001406836.1	c.386+4828A>G		intron_variant			NP_001393765.1
KCNQ1	NM_001406837.1	c.24+4828A>G		intron_variant			NP_001393766.1
KCNQ1	NM_001406838.1	c.386+4828A>G		intron_variant			NP_001393767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+4828A>G		intron_variant		1	NM_000218.3	ENSP00000155840.2
KCNQ1	ENST00000345015.4	n.163+4828A>G		intron_variant		1
KCNQ1	ENST00000496887.7	c.125+4828A>G		intron_variant		5		ENSP00000434560.2
KCNQ1	ENST00000646564.2	c.386+4828A>G		intron_variant				ENSP00000495806.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43361 AN: 151940 Hom.: 8705 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.286 AC: 43441 AN: 152058 Hom.: 8729 Cov.: 33 AF XY: 0.287 AC XY: 21352 AN XY: 74318

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.274

Alfa AF: 0.0994 Hom.: 223

Bravo AF: 0.306

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.0
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2023818; hg19: chr11-2471542;