rs2267386

Positions:

• chr22-38436107-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNJ4	NM_152868.3	c.-39-7936C>T		intron_variant		ENST00000303592.3	NP_690607.1
LOC105373029	XR_938251.3	n.179-196G>A		intron_variant, non_coding_transcript_variant
KCNJ4	NM_004981.2	c.-40+7864C>T		intron_variant			NP_004972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ4	ENST00000303592.3	c.-39-7936C>T		intron_variant		1	NM_152868.3	ENSP00000306497	P1
	ENST00000662373.1	n.237-196G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.0381

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0338

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0327 Hom.: 21

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267386; hg19: chr22-38832112;