11-2848222-G-T

Variant names:

• chr11-2848222-G-T
• rs45477500
• NM_000218.3:c.*219G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000218.3(KCNQ1):​c.*219G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 510,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: KCNQ1 NM_000218.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• 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-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	NM_000218.3	MANE Select	c.*219G>T		3_prime_UTR	Exon 16 of 16	NP_000209.2
	KCNQ1	NM_001406836.1		c.*219G>T		3_prime_UTR	Exon 15 of 15	NP_001393765.1
	KCNQ1	NM_001406837.1		c.*219G>T		3_prime_UTR	Exon 17 of 17	NP_001393766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.*219G>T		3_prime_UTR	Exon 16 of 16	ENSP00000155840.2
	KCNQ1	ENST00000335475.6	TSL:1	c.*219G>T		3_prime_UTR	Exon 16 of 16	ENSP00000334497.5
	KCNQ1	ENST00000713724.1		n.*2216G>T		non_coding_transcript_exon	Exon 16 of 16	ENSP00000519028.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000196 AC: 1 AN: 510044 Hom.: 0 Cov.: 3 AF XY: 0.00000365 AC XY: 1 AN XY: 273622

African (AFR) AF: 0.00 AC: 0 AN: 14576

American (AMR) AF: 0.00 AC: 0 AN: 29934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17412

East Asian (EAS) AF: 0.00 AC: 0 AN: 31528

South Asian (SAS) AF: 0.00 AC: 0 AN: 56428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2258

European-Non Finnish (NFE) AF: 0.00000336 AC: 1 AN: 297766

Other (OTH) AF: 0.00 AC: 0 AN: 28452

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.2
DANN	Benign	0.86
PhyloP100		0.22

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: rs45477500; hg19: chr11-2869452;