chr22-38426693-C-T

Position:

• chr22-38426693-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152868.3(KCNJ4):​c.*102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,410,770 control chromosomes in the GnomAD database, including 30,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2595 hom., cov: 31)
  • Exomes 𝑓: 0.20 (27694 hom.)
• Consequence: KCNJ4 NM_152868.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.39

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-38426693-C-T is Benign according to our data. Variant chr22-38426693-C-T is described in ClinVar as [Benign]. Clinvar id is 1281966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ4	NM_152868.3	c.*102G>A		3_prime_UTR_variant	2/2	ENST00000303592.3
LOC101927183	XR_938252.3	n.306+1721C>T		intron_variant, non_coding_transcript_variant
KCNJ4	NM_004981.2	c.*102G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ4	ENST00000303592.3	c.*102G>A		3_prime_UTR_variant	2/2	1	NM_152868.3	P1
	ENST00000433230.1	n.297-384C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24963 AN: 151954 Hom.: 2591 Cov.: 31

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.204 AC: 257241 AN: 1258698 Hom.: 27694 Cov.: 19 AF XY: 0.204 AC XY: 126636 AN XY: 619618

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.164 AC: 24965 AN: 152072 Hom.: 2595 Cov.: 31 AF XY: 0.171 AC XY: 12673 AN XY: 74318

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.175

Alfa AF: 0.188 Hom.: 2820

Bravo AF: 0.146

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.69

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: rs1063134; hg19: chr22-38822698; COSMIC: COSV57856756;