rs196072

Variant names:

• chr22-38435807-T-C
• rs196072
• NM_152868.3:c.-39-7636A>G

Variant summary

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

The NM_152868.3(KCNJ4):​c.-39-7636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,130 control chromosomes in the GnomAD database, including 841 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 0.088 (841 hom., cov: 32)
• Consequence: KCNJ4 NM_152868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 2 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]

ENSG00000286440 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.-39-7636A>G		intron	N/A	NP_690607.1	P48050
	KCNJ4	NM_004981.2		c.-39-7636A>G		intron	N/A	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.-39-7636A>G		intron	N/A	ENSP00000306497.3	P48050
	KCNJ4	ENST00000940563.1		c.-40+1571A>G		intron	N/A	ENSP00000610622.1
	KCNJ4	ENST00000947103.1		c.-22-7653A>G		intron	N/A	ENSP00000617162.1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13404 AN: 152020 Hom.: 842 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.0882 AC: 13418 AN: 152130 Hom.: 841 Cov.: 32 AF XY: 0.0840 AC XY: 6247 AN XY: 74388

African (AFR) AF: 0.183 AC: 7572 AN: 41488

American (AMR) AF: 0.0528 AC: 807 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4820

European-Finnish (FIN) AF: 0.0200 AC: 212 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4074 AN: 67980

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.107 Hom.: 445

Bravo AF: 0.0961

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.35
PhyloP100		-1.2
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: rs196072; hg19: chr22-38831812;