rs944443085

Variant names:

• chr11-2444984-GC-G
• rs944443085
• ENST00000713725.1:c.-109delC

Your query was ambiguous. Multiple possible variants found:

• chr11-2444984-GC-G
• chr11-2444984-GC-GCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000713725.1(KCNQ1):​c.-109delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 547,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: KCNQ1 ENST00000713725.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.943
• Publications: 0 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 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Jervell and Lange-Nielsen syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• long QT syndrome 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• atrial fibrillation, familial, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short QT syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• short QT syndrome type 2

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 11-2444984-GC-G is Benign according to our data. Variant chr11-2444984-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1225723.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000713725.1. 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.-114delC		upstream_gene	N/A	NP_000209.2
	KCNQ1	NM_001406836.1		c.-114delC		upstream_gene	N/A	NP_001393765.1
	KCNQ1	NM_001406837.1		c.-476delC		upstream_gene	N/A	NP_001393766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000713725.1		c.-109delC		5_prime_UTR	Exon 1 of 15	ENSP00000519029.1	A0AAQ5BGS5
	KCNQ1	ENST00000496887.7	TSL:5	c.23+282delC		intron	N/A	ENSP00000434560.2	E9PPZ0
	KCNQ1	ENST00000713724.1		n.-109delC		non_coding_transcript_exon	Exon 1 of 16	ENSP00000519028.1	A0AAQ5BGV1

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 30 AN: 146538 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000496

GnomAD4 exome AF: 0.0000299 AC: 12 AN: 401062 Hom.: 0 Cov.: 5 AF XY: 0.0000264 AC XY: 5 AN XY: 189386

African (AFR) AF: 0.00107 AC: 8 AN: 7448

American (AMR) AF: 0.00 AC: 0 AN: 938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2698

East Asian (EAS) AF: 0.00 AC: 0 AN: 2086

South Asian (SAS) AF: 0.00 AC: 0 AN: 8060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 838

European-Non Finnish (NFE) AF: 0.0000110 AC: 4 AN: 363774

Other (OTH) AF: 0.00 AC: 0 AN: 13556

GnomAD4 genome AF: 0.000205 AC: 30 AN: 146538 Hom.: 0 Cov.: 32 AF XY: 0.000196 AC XY: 14 AN XY: 71258

African (AFR) AF: 0.000686 AC: 28 AN: 40792

American (AMR) AF: 0.0000675 AC: 1 AN: 14804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5004

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65862

Other (OTH) AF: 0.000496 AC: 1 AN: 2016

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000280

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs944443085; hg19: chr11-2466214;