11-2840348-G-T

Position:

• chr11-2840348-G-T

Variant summary

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

The NM_000218.3(KCNQ1):​c.1795-7419G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,078 control chromosomes in the GnomAD database, including 12,224 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 0.39 (12200 hom., cov: 31)
  • Exomes 𝑓: 0.44 (24 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-7419G>T		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1795-7419G>T		intron_variant		1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59026 AN: 151696 Hom.: 12197 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.436 AC: 115 AN: 264 Hom.: 24 Cov.: 0 AF XY: 0.474 AC XY: 74 AN XY: 156

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.389 AC: 59049 AN: 151814 Hom.: 12200 Cov.: 31 AF XY: 0.386 AC XY: 28666 AN XY: 74186

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.446

Alfa AF: 0.447 Hom.: 21113

Bravo AF: 0.375

Asia WGS AF: 0.362 AC: 1259 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.61

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: rs10741726; hg19: chr11-2861578;