22-38446037-T-C

Variant names:

• chr22-38446037-T-C
• rs196084
• NM_152868.3:c.-40+8943A>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.-40+8943A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,118 control chromosomes in the GnomAD database, including 37,859 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 0.70 (37859 hom., cov: 32)
• Consequence: KCNJ4 NM_152868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ4	NM_152868.3	c.-40+8943A>G		intron_variant	Intron 1 of 1	ENST00000303592.3	NP_690607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ4	ENST00000303592.3	c.-40+8943A>G		intron_variant	Intron 1 of 1	1	NM_152868.3	ENSP00000306497.3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106107 AN: 152000 Hom.: 37804 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.698 AC: 106218 AN: 152118 Hom.: 37859 Cov.: 32 AF XY: 0.705 AC XY: 52401 AN XY: 74372

African (AFR) AF: 0.805 AC: 33411 AN: 41482

American (AMR) AF: 0.676 AC: 10332 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3470

East Asian (EAS) AF: 0.934 AC: 4833 AN: 5174

South Asian (SAS) AF: 0.877 AC: 4235 AN: 4828

European-Finnish (FIN) AF: 0.673 AC: 7129 AN: 10590

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41865 AN: 67964

Other (OTH) AF: 0.701 AC: 1481 AN: 2112

Alfa AF: 0.659 Hom.: 7604

Bravo AF: 0.700

Asia WGS AF: 0.905 AC: 3147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.39
PhyloP100		0.42
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: rs196084; hg19: chr22-38842042;