2-42440445-T-G

Variant names:

• chr2-42440445-T-G
• rs1874449
• XR_007069666.1:n.1187+4061A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007069666.1(KCNG3):​n.1187+4061A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 149,954 control chromosomes in the GnomAD database, including 12,758 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 0.40 (12757 hom., cov: 27)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: KCNG3 XR_007069666.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522
• Publications: 3 publications found

Genes affected

KCNG3 (HGNC:18306): (potassium voltage-gated channel modifier subfamily G member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit functioning as a modulatory molecule. Alternative splicing results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000221300 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000408373.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000221300	ENST00000408373.1	TSL:6	n.*9T>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.404 AC: 60514 AN: 149832 Hom.: 12744 Cov.: 27

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.404 AC: 60565 AN: 149942 Hom.: 12757 Cov.: 27 AF XY: 0.405 AC XY: 29599 AN XY: 73008

African (AFR) AF: 0.313 AC: 12781 AN: 40816

American (AMR) AF: 0.310 AC: 4662 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1678 AN: 3460

East Asian (EAS) AF: 0.598 AC: 3053 AN: 5108

South Asian (SAS) AF: 0.412 AC: 1948 AN: 4732

European-Finnish (FIN) AF: 0.483 AC: 4768 AN: 9862

Middle Eastern (MID) AF: 0.399 AC: 115 AN: 288

European-Non Finnish (NFE) AF: 0.447 AC: 30224 AN: 67620

Other (OTH) AF: 0.419 AC: 879 AN: 2098

Alfa AF: 0.304 Hom.: 980

Bravo AF: 0.387

Asia WGS AF: 0.438 AC: 1521 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.7
DANN	Benign	0.86
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs1874449; hg19: chr2-42667585;