NM_002241.5:c.1-84T>C

Variant names:

• chr1-160042616-A-G
• rs12729701
• NM_002241.5:c.1-84T>C

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.1-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,177,116 control chromosomes in the GnomAD database, including 36,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3413 hom., cov: 32)
  • Exomes 𝑓: 0.24 (32689 hom.)
• Consequence: KCNJ10 NM_002241.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.295
• Publications: 8 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=-0.91).
• BP6: Variant 1-160042616-A-G is Benign according to our data. Variant chr1-160042616-A-G is described in ClinVar as [Benign]. Clinvar id is 1291083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ10	NM_002241.5	c.1-84T>C		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.1-84T>C		intron_variant	Intron 1 of 1		NM_002241.5	ENSP00000495557.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29323 AN: 152014 Hom.: 3416 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.245 AC: 251015 AN: 1024984 Hom.: 32689 AF XY: 0.249 AC XY: 131672 AN XY: 527998

African (AFR) AF: 0.0667 AC: 1687 AN: 25308

American (AMR) AF: 0.131 AC: 5509 AN: 42046

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4375 AN: 23360

East Asian (EAS) AF: 0.246 AC: 9171 AN: 37344

South Asian (SAS) AF: 0.334 AC: 25331 AN: 75940

European-Finnish (FIN) AF: 0.206 AC: 8865 AN: 43058

Middle Eastern (MID) AF: 0.232 AC: 1155 AN: 4972

European-Non Finnish (NFE) AF: 0.253 AC: 183975 AN: 726816

Other (OTH) AF: 0.237 AC: 10947 AN: 46140

GnomAD4 genome AF: 0.193 AC: 29324 AN: 152132 Hom.: 3413 Cov.: 32 AF XY: 0.192 AC XY: 14290 AN XY: 74344

African (AFR) AF: 0.0725 AC: 3010 AN: 41530

American (AMR) AF: 0.171 AC: 2612 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1249 AN: 5164

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4812

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10568

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17327 AN: 67986

Other (OTH) AF: 0.210 AC: 444 AN: 2110

Alfa AF: 0.216 Hom.: 644

Bravo AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.51
PhyloP100		-0.29
PromoterAI		-0.0058	Neutral
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: rs12729701; hg19: chr1-160012406; COSMIC: COSV63634024; COSMIC: COSV63634024;