rs3864884

Variant names:

• chr11-2460862-C-T
• rs3864884
• NM_000218.3:c.386+15378C>T

Variant summary

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

The NM_000218.3(KCNQ1):​c.386+15378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,160 control chromosomes in the GnomAD database, including 8,070 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 0.30 (8070 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.386+15378C>T		intron_variant	Intron 1 of 15	ENST00000155840.12	NP_000209.2
KCNQ1	NM_001406836.1	c.386+15378C>T		intron_variant	Intron 1 of 14		NP_001393765.1
KCNQ1	NM_001406837.1	c.24+15378C>T		intron_variant	Intron 1 of 16		NP_001393766.1
KCNQ1	NM_001406838.1	c.386+15378C>T		intron_variant	Intron 1 of 10		NP_001393767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.386+15378C>T		intron_variant	Intron 1 of 15	1	NM_000218.3	ENSP00000155840.2
KCNQ1	ENST00000345015.4	n.163+15378C>T		intron_variant	Intron 1 of 2	1
KCNQ1	ENST00000496887.7	c.125+15378C>T		intron_variant	Intron 2 of 15	5		ENSP00000434560.2
KCNQ1	ENST00000646564.2	c.386+15378C>T		intron_variant	Intron 1 of 10			ENSP00000495806.2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44977 AN: 152042 Hom.: 8023 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.296 AC: 45084 AN: 152160 Hom.: 8070 Cov.: 33 AF XY: 0.302 AC XY: 22481 AN XY: 74374

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.271

Alfa AF: 0.204 Hom.: 5234

Bravo AF: 0.311

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.54

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: rs3864884; hg19: chr11-2482092;