NM_000218.3:c.1795-33217A>G

Variant names:

• chr11-2814550-A-G
• rs123381
• NM_000218.3:c.1795-33217A>G

Variant summary

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

The NM_000218.3(KCNQ1):​c.1795-33217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 148,624 control chromosomes in the GnomAD database, including 32,577 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 0.65 (32577 hom., cov: 25)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-33217A>G		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.1795-33217A>G		intron_variant	Intron 15 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 97050 AN: 148510 Hom.: 32557 Cov.: 25

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.653 AC: 97104 AN: 148624 Hom.: 32577 Cov.: 25 AF XY: 0.656 AC XY: 47560 AN XY: 72508

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.638

Alfa AF: 0.696 Hom.: 7338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.36

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: rs123381; hg19: chr11-2835780;