11-2840348-G-T

Variant names:

• chr11-2840348-G-T
• rs10741726
• NM_000218.3:c.1795-7419G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000218.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	NM_000218.3	MANE Select	c.1795-7419G>T		intron	N/A	NP_000209.2
	KCNQ1	NM_001406836.1		c.1699-7419G>T		intron	N/A	NP_001393765.1
	KCNQ1	NM_001406837.1		c.1525-7419G>T		intron	N/A	NP_001393766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.1795-7419G>T		intron	N/A	ENSP00000155840.2	P51787-1
	KCNQ1	ENST00000335475.6	TSL:1	c.1414-7419G>T		intron	N/A	ENSP00000334497.5	P51787-2
	KCNQ1	ENST00000910997.1		c.1792-7419G>T		intron	N/A	ENSP00000581056.1

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.372 AC: 61 AN: 164

Middle Eastern (MID) AF: 0.559 AC: 38 AN: 68

European-Non Finnish (NFE) AF: 0.583 AC: 7 AN: 12

Other (OTH) AF: 0.438 AC: 7 AN: 16

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

African (AFR) AF: 0.285 AC: 11779 AN: 41392

American (AMR) AF: 0.333 AC: 5068 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5164

South Asian (SAS) AF: 0.528 AC: 2533 AN: 4800

European-Finnish (FIN) AF: 0.387 AC: 4077 AN: 10534

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31464 AN: 67914

Other (OTH) AF: 0.446 AC: 939 AN: 2106

Alfa AF: 0.439 Hom.: 28224

Bravo AF: 0.375

Asia WGS AF: 0.362 AC: 1259 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.61
PhyloP100		-1.4
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: rs10741726; hg19: chr11-2861578;