chr1-160063712-C-T

Position:

• chr1-160063712-C-T

Variant summary

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

The NM_002241.5(KCNJ10):​c.-1+6310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,152 control chromosomes in the GnomAD database, including 24,619 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 0.56 (24612 hom., cov: 32)
  • Exomes 𝑓: 0.55 (7 hom.)
• Consequence: KCNJ10 NM_002241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

Genes affected

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ10	NM_002241.5	c.-1+6310G>A		intron_variant		ENST00000644903.1	NP_002232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ10	ENST00000644903.1	c.-1+6310G>A		intron_variant			NM_002241.5	ENSP00000495557	P1
	ENST00000435580.2	n.271+123C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85869 AN: 151992 Hom.: 24596 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.548 AC: 23 AN: 42 Hom.: 7 AF XY: 0.531 AC XY: 17 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.565 AC: 85922 AN: 152110 Hom.: 24612 Cov.: 32 AF XY: 0.565 AC XY: 42034 AN XY: 74344

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.582

Alfa AF: 0.543 Hom.: 21926

Bravo AF: 0.578

Asia WGS AF: 0.695 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs6690889; hg19: chr1-160033502;