rs1053074

Variant names:

• chr1-160039331-A-C
• rs1053074
• NM_002241.5:c.*2062T>G

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.*2062T>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 0.456 in 151,462 control chromosomes in the GnomAD database, including 16,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16616 hom., cov: 28)
  • Exomes 𝑓: 0.36 (80 hom.)
• Consequence: KCNJ10 NM_002241.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.67
• Publications: 17 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: G2P, Orphanet, Ambry Genetics, 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=-0.58).
• BP6: Variant 1-160039331-A-C is Benign according to our data. Variant chr1-160039331-A-C is described in ClinVar as Benign. ClinVar VariationId is 293090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ10	NM_002241.5	MANE Select	c.*2062T>G		3_prime_UTR	Exon 2 of 2	NP_002232.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ10	ENST00000644903.1	MANE Select	c.*2062T>G		3_prime_UTR	Exon 2 of 2	ENSP00000495557.1	P78508
	KCNJ10	ENST00000638728.1	TSL:5	c.*2062T>G		3_prime_UTR	Exon 3 of 3	ENSP00000492619.1	P78508
	KCNJ10	ENST00000638868.1	TSL:5	c.*2062T>G		3_prime_UTR	Exon 3 of 3	ENSP00000491250.1	P78508

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68675 AN: 150496 Hom.: 16600 Cov.: 28

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.365 AC: 310 AN: 850 Hom.: 80 Cov.: 0 AF XY: 0.355 AC XY: 210 AN XY: 592

African (AFR) AF: 0.667 AC: 8 AN: 12

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.0500 AC: 1 AN: 20

South Asian (SAS) AF: 0.500 AC: 5 AN: 10

European-Finnish (FIN) AF: 0.358 AC: 128 AN: 358

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.367 AC: 151 AN: 412

Other (OTH) AF: 0.500 AC: 14 AN: 28

GnomAD4 genome AF: 0.456 AC: 68736 AN: 150612 Hom.: 16616 Cov.: 28 AF XY: 0.452 AC XY: 33245 AN XY: 73510

African (AFR) AF: 0.613 AC: 25024 AN: 40790

American (AMR) AF: 0.442 AC: 6691 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3466

East Asian (EAS) AF: 0.335 AC: 1711 AN: 5112

South Asian (SAS) AF: 0.470 AC: 2221 AN: 4726

European-Finnish (FIN) AF: 0.334 AC: 3451 AN: 10332

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 26998 AN: 67772

Other (OTH) AF: 0.418 AC: 875 AN: 2092

Alfa AF: 0.417 Hom.: 23065

Bravo AF: 0.467

Asia WGS AF: 0.394 AC: 1363 AN: 3468

ClinVar

ClinVar submissions

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	-0.58
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		1.7
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: rs1053074; hg19: chr1-160009121; COSMIC: COSV63635370;