chr22-38426693-C-T

Variant names:

• chr22-38426693-C-T
• rs1063134
• NM_152868.3:c.*102G>A

Variant summary

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

The NM_152868.3(KCNJ4):​c.*102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,410,770 control chromosomes in the GnomAD database, including 30,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2595 hom., cov: 31)
  • Exomes 𝑓: 0.20 (27694 hom.)
• Consequence: KCNJ4 NM_152868.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.39
• Publications: 9 publications found

Genes affected

KCNJ4 (HGNC:6265): (potassium inwardly rectifying channel subfamily J member 4) Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000228620 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-38426693-C-T is Benign according to our data. Variant chr22-38426693-C-T is described in ClinVar as Benign. ClinVar VariationId is 1281966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152868.3. 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
	KCNJ4	NM_152868.3	MANE Select	c.*102G>A		3_prime_UTR	Exon 2 of 2	NP_690607.1	P48050
	KCNJ4	NM_004981.2		c.*102G>A		3_prime_UTR	Exon 2 of 2	NP_004972.1	P48050

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ4	ENST00000303592.3	TSL:1 MANE Select	c.*102G>A		3_prime_UTR	Exon 2 of 2	ENSP00000306497.3	P48050
	KCNJ4	ENST00000940563.1		c.*102G>A		3_prime_UTR	Exon 2 of 2	ENSP00000610622.1
	KCNJ4	ENST00000947103.1		c.*102G>A		3_prime_UTR	Exon 2 of 2	ENSP00000617162.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24963 AN: 151954 Hom.: 2591 Cov.: 31

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.204 AC: 257241 AN: 1258698 Hom.: 27694 Cov.: 19 AF XY: 0.204 AC XY: 126636 AN XY: 619618

African (AFR) AF: 0.0325 AC: 914 AN: 28120

American (AMR) AF: 0.100 AC: 2877 AN: 28748

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 3913 AN: 19234

East Asian (EAS) AF: 0.229 AC: 8722 AN: 38112

South Asian (SAS) AF: 0.180 AC: 12132 AN: 67286

European-Finnish (FIN) AF: 0.327 AC: 15907 AN: 48618

Middle Eastern (MID) AF: 0.181 AC: 723 AN: 3998

European-Non Finnish (NFE) AF: 0.207 AC: 201508 AN: 972008

Other (OTH) AF: 0.201 AC: 10545 AN: 52574

GnomAD4 genome AF: 0.164 AC: 24965 AN: 152072 Hom.: 2595 Cov.: 31 AF XY: 0.171 AC XY: 12673 AN XY: 74318

African (AFR) AF: 0.0409 AC: 1698 AN: 41534

American (AMR) AF: 0.142 AC: 2164 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 747 AN: 3464

East Asian (EAS) AF: 0.228 AC: 1173 AN: 5146

South Asian (SAS) AF: 0.184 AC: 886 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3583 AN: 10570

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14015 AN: 67942

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.187 Hom.: 3391

Bravo AF: 0.146

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.69
PhyloP100		-3.4
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: rs1063134; hg19: chr22-38822698; COSMIC: COSV57856756;