1-160050447-T-C

Variant names:

• chr1-160050447-T-C
• rs12402969
• NM_002241.5:c.1-7915A>G

Variant summary

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

The NM_002241.5(KCNJ10):​c.1-7915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,176 control chromosomes in the GnomAD database, including 1,154 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 0.11 (1154 hom., cov: 31)
• Consequence: KCNJ10 NM_002241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 3 publications found

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]

KCNJ10 Gene-Disease associations (from GenCC):

• EAST syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Pendred syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• enlarged vestibular aqueduct syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ10	NM_002241.5	c.1-7915A>G		intron_variant	Intron 1 of 1	ENST00000644903.1	NP_002232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ10	ENST00000644903.1	c.1-7915A>G		intron_variant	Intron 1 of 1		NM_002241.5	ENSP00000495557.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16172 AN: 152058 Hom.: 1153 Cov.: 31

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16180 AN: 152176 Hom.: 1154 Cov.: 31 AF XY: 0.108 AC XY: 8037 AN XY: 74402

African (AFR) AF: 0.0259 AC: 1076 AN: 41534

American (AMR) AF: 0.155 AC: 2375 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.0876 AC: 454 AN: 5184

South Asian (SAS) AF: 0.0763 AC: 368 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1708 AN: 10594

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.138 AC: 9361 AN: 67966

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.0974 Hom.: 390

Bravo AF: 0.102

Asia WGS AF: 0.0900 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

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: rs12402969; hg19: chr1-160020237;