11-2848482-G-A

Variant names:

• chr11-2848482-G-A
• rs2519184
• NM_000218.3:c.*479G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):​c.*479G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 457,636 control chromosomes in the GnomAD database, including 3,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (945 hom., cov: 34)
  • Exomes 𝑓: 0.11 (2450 hom.)
• Consequence: KCNQ1 NM_000218.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0380
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-2848482-G-A is Benign according to our data. Variant chr11-2848482-G-A is described in ClinVar as Benign. ClinVar VariationId is 304249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 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.*479G>A		3_prime_UTR	Exon 16 of 16	NP_000209.2
	KCNQ1	NM_001406836.1		c.*479G>A		3_prime_UTR	Exon 15 of 15	NP_001393765.1
	KCNQ1	NM_001406837.1		c.*479G>A		3_prime_UTR	Exon 17 of 17	NP_001393766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.*479G>A		3_prime_UTR	Exon 16 of 16	ENSP00000155840.2	P51787-1
	KCNQ1	ENST00000335475.6	TSL:1	c.*479G>A		3_prime_UTR	Exon 16 of 16	ENSP00000334497.5	P51787-2
	KCNQ1	ENST00000910997.1		c.*479G>A		3_prime_UTR	Exon 16 of 16	ENSP00000581056.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15675 AN: 152098 Hom.: 944 Cov.: 34

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.125 AC: 16412 AN: 131708 AF XY: 0.117

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.0659

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.0929

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.109 AC: 33366 AN: 305420 Hom.: 2450 Cov.: 0 AF XY: 0.105 AC XY: 18242 AN XY: 173828

African (AFR) AF: 0.101 AC: 881 AN: 8692

American (AMR) AF: 0.263 AC: 7200 AN: 27342

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 1036 AN: 10954

East Asian (EAS) AF: 0.0642 AC: 600 AN: 9352

South Asian (SAS) AF: 0.0930 AC: 5546 AN: 59658

European-Finnish (FIN) AF: 0.121 AC: 1534 AN: 12640

Middle Eastern (MID) AF: 0.0938 AC: 109 AN: 1162

European-Non Finnish (NFE) AF: 0.0934 AC: 15068 AN: 161294

Other (OTH) AF: 0.0972 AC: 1392 AN: 14326

GnomAD4 genome AF: 0.103 AC: 15694 AN: 152216 Hom.: 945 Cov.: 34 AF XY: 0.105 AC XY: 7826 AN XY: 74424

African (AFR) AF: 0.0974 AC: 4044 AN: 41528

American (AMR) AF: 0.170 AC: 2606 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.0596 AC: 309 AN: 5186

South Asian (SAS) AF: 0.0860 AC: 415 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6290 AN: 67978

Other (OTH) AF: 0.105 AC: 223 AN: 2116

Alfa AF: 0.0698 Hom.: 118

Bravo AF: 0.108

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atrial fibrillation, familial, 3 (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Jervell and Lange-Nielsen syndrome 1 (1)
-	-	1	Long QT syndrome (1)
-	-	1	Long QT syndrome 1 (1)
-	-	1	Short QT syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		0.038
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: rs2519184; hg19: chr11-2869712;