rs196072

chr22-38435807-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ4	NM_152868.3	c.-39-7636A>G		intron_variant		ENST00000303592.3
LOC105373029	XR_938251.3	n.179-496T>C		intron_variant, non_coding_transcript_variant
KCNJ4	NM_004981.2	c.-39-7636A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ4	ENST00000303592.3	c.-39-7636A>G		intron_variant		1	NM_152868.3	P1
	ENST00000662373.1	n.237-496T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0804 Hom.: 88

Bravo AF: 0.0961

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.63
Dann	Benign	0.35

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: rs196072; hg19: chr22-38831812;