2-42440445-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007069666.1(KCNG3):n.1187+4061A>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

Genes affected

KCNG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNG3	XR_007069666.1	n.1187+4061A>C		intron_variant, non_coding_transcript_variant
LOC124900542	XR_007088733.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000408373.1			downstream_gene_variant

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

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.419

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	7.7
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1874449; hg19: chr2-42667585;