rs76457020

Variant names:

• chr17-70169388-G-A
• rs76457020
• ENST00000535240.1:c.-217+531G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-70169388-G-A
• chr17-70169388-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000535240.1(KCNJ2):​c.-217+531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,952 control chromosomes in the GnomAD database, including 1,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1105 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ2 ENST00000535240.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0190
• Publications: 3 publications found

Genes affected

KCNJ2 (HGNC:6263): (potassium inwardly rectifying channel subfamily J member 2) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Mutations in this gene have been associated with Andersen syndrome, which is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. [provided by RefSeq, Jul 2008]

KCNJ2-AS1 (HGNC:43720): (KCNJ2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-70169388-G-A is Benign according to our data. Variant chr17-70169388-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535240.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ2-AS1	NR_036534.1		n.15C>T		non_coding_transcript_exon	Exon 1 of 1
	KCNJ2	NM_000891.3	MANE Select	c.-530G>A		upstream_gene	N/A	NP_000882.1	P63252

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ2	ENST00000535240.1	TSL:1	c.-217+531G>A		intron	N/A	ENSP00000441848.1	P63252
	KCNJ2	ENST00000854891.1		c.-217+531G>A		intron	N/A	ENSP00000524950.1
	KCNJ2	ENST00000854892.1		c.-217+531G>A		intron	N/A	ENSP00000524951.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17995 AN: 151844 Hom.: 1106 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.126

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.119 AC: 18011 AN: 151952 Hom.: 1105 Cov.: 32 AF XY: 0.120 AC XY: 8904 AN XY: 74280

African (AFR) AF: 0.105 AC: 4352 AN: 41500

American (AMR) AF: 0.183 AC: 2793 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3468

East Asian (EAS) AF: 0.0893 AC: 453 AN: 5072

South Asian (SAS) AF: 0.178 AC: 862 AN: 4830

European-Finnish (FIN) AF: 0.0926 AC: 980 AN: 10584

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7738 AN: 67916

Other (OTH) AF: 0.124 AC: 262 AN: 2110

Alfa AF: 0.0439 Hom.: 41

Bravo AF: 0.125

Asia WGS AF: 0.115 AC: 398 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		-0.019
PromoterAI		-0.27	Neutral
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: rs76457020; hg19: chr17-68165529;