chr22-38436107-G-A

Variant names:

• chr22-38436107-G-A
• rs2267386
• NM_152868.3:c.-39-7936C>T

Variant summary

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

The NM_152868.3(KCNJ4):​c.-39-7936C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 152,226 control chromosomes in the GnomAD database, including 103 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 0.029 (103 hom., cov: 32)
• Consequence: KCNJ4 NM_152868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ4	NM_152868.3	c.-39-7936C>T		intron_variant	Intron 1 of 1	ENST00000303592.3	NP_690607.1
KCNJ4	NM_004981.2	c.-40+7864C>T		intron_variant	Intron 1 of 1		NP_004972.1
LOC105373029	XR_938251.3	n.179-196G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ4	ENST00000303592.3	c.-39-7936C>T		intron_variant	Intron 1 of 1	1	NM_152868.3	ENSP00000306497.3
ENSG00000286440	ENST00000662373.1	n.237-196G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4412 AN: 152108 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0254

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

GnomAD4 genome AF: 0.0290 AC: 4411 AN: 152226 Hom.: 103 Cov.: 32 AF XY: 0.0296 AC XY: 2203 AN XY: 74426

African (AFR) AF: 0.00700 AC: 291 AN: 41548

American (AMR) AF: 0.0381 AC: 583 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3468

East Asian (EAS) AF: 0.122 AC: 631 AN: 5172

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.0417 AC: 442 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0338 AC: 2298 AN: 68002

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0372 Hom.: 222

Bravo AF: 0.0295

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		0.051
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: rs2267386; hg19: chr22-38832112;