chr21-38299277-A-G

Position:

• chr21-38299277-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_170736.3(KCNJ15):​c.16A>G​(p.Ile6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,612,450 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (14 hom., cov: 33)
  • Exomes 𝑓: 0.011 (127 hom.)
• Consequence: KCNJ15 NM_170736.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.224

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) 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 has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032828748).
• BP6: Variant 21-38299277-A-G is Benign according to our data. Variant chr21-38299277-A-G is described in ClinVar as [Benign]. Clinvar id is 770817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.16A>G	p.Ile6Val	missense_variant	3/3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.16A>G	p.Ile6Val	missense_variant	3/3	1	NM_170736.3	ENSP00000381911	P1

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1164 AN: 152184 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00854 AC: 2132 AN: 249750 Hom.: 21 AF XY: 0.00877 AC XY: 1184 AN XY: 134982

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00250

Gnomad ASJ exome AF: 0.0373

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00255

Gnomad FIN exome AF: 0.00455

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0115

GnomAD4 exome AF: 0.0106 AC: 15522 AN: 1460148 Hom.: 127 Cov.: 31 AF XY: 0.0107 AC XY: 7736 AN XY: 726144

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.00766 AC: 1166 AN: 152302 Hom.: 14 Cov.: 33 AF XY: 0.00691 AC XY: 515 AN XY: 74480

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0124 Hom.: 19

Bravo AF: 0.00763

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0126 AC: 108

ExAC AF: 0.00876 AC: 1063

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0112

EpiControl AF: 0.0118

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.0050
DANN	Benign	0.26
DEOGEN2	Benign	0.027	T;.;.;.;.;.;.;T;T;.;T;T;T;T;T;T;.;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.50	T;.;.;.;.;.;T;.;T;T;.;.;T;.;.;.;T;.;.;T;T
MetaRNN	Benign	0.0033	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.49	.;.;.;.;.;.;.;N;N;.;.;N;.;.;N;N;.;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.82	N;N;N;N;N;N;N;.;.;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.51	.;T;T;T;T;T;T;.;.;T;T;T;T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T
Polyphen		0.0	.;.;.;.;.;.;.;B;B;.;.;B;.;.;B;B;.;B;B;.;.
Vest4		0.045, 0.069, 0.059, 0.055, 0.060
MVP		0.63
MPC		0.37
ClinPred		0.0013	T
GERP RS		-2.5
Varity_R		0.028
gMVP		0.66

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: rs79109585; hg19: chr21-39671199;