rs2486253

Variant names:

• chr1-160039629-A-C
• rs2486253
• NM_002241.5:c.*1764T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-160039629-A-C
• chr1-160039629-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002241.5(KCNJ10):​c.*1764T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,136 control chromosomes in the GnomAD database, including 51,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51109 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KCNJ10 NM_002241.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.282
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-160039629-A-C is Benign according to our data. Variant chr1-160039629-A-C is described in ClinVar as Benign. ClinVar VariationId is 293102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002241.5. 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
	KCNJ10	NM_002241.5	MANE Select	c.*1764T>G		3_prime_UTR	Exon 2 of 2	NP_002232.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ10	ENST00000644903.1	MANE Select	c.*1764T>G		3_prime_UTR	Exon 2 of 2	ENSP00000495557.1
	KCNJ10	ENST00000638840.1	TSL:5	n.*1030T>G		non_coding_transcript_exon	Exon 2 of 2	ENSP00000492249.1
	KCNJ10	ENST00000638728.1	TSL:5	c.*1764T>G		3_prime_UTR	Exon 3 of 3	ENSP00000492619.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124479 AN: 152014 Hom.: 51070 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

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: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.819 AC: 124576 AN: 152132 Hom.: 51109 Cov.: 31 AF XY: 0.822 AC XY: 61097 AN XY: 74356

African (AFR) AF: 0.818 AC: 33938 AN: 41486

American (AMR) AF: 0.826 AC: 12627 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2771 AN: 3470

East Asian (EAS) AF: 0.961 AC: 4973 AN: 5174

South Asian (SAS) AF: 0.824 AC: 3968 AN: 4816

European-Finnish (FIN) AF: 0.841 AC: 8898 AN: 10580

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54764 AN: 68002

Other (OTH) AF: 0.816 AC: 1724 AN: 2114

Alfa AF: 0.809 Hom.: 87657

Bravo AF: 0.819

Asia WGS AF: 0.866 AC: 3008 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 4 (1)
-	-	1	EAST syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.76
PhyloP100		0.28
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: rs2486253; hg19: chr1-160009419; COSMIC: COSV105294526;