chr11-128900463-G-T

Variant names:

• chr11-128900463-G-T
• rs3740835
• ENST00000310799.9:n.2726C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000310799.9(KCNJ5-AS1):​n.2726C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,162 control chromosomes in the GnomAD database, including 1,113 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 0.084 (1113 hom., cov: 33)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: KCNJ5-AS1 ENST00000310799.9 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 5 publications found

Genes affected

KCNJ5-AS1 (HGNC:28584): (KCNJ5 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 Gene-Disease associations (from GenCC):

• familial hyperaldosteronism type III

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• Andersen-Tawil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310799.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	NM_000890.5	MANE Select	c.-11+8742G>T		intron	N/A	NP_000881.3
	KCNJ5-AS1	NR_045767.1		n.2660C>A		non_coding_transcript_exon	Exon 4 of 4
	KCNJ5-AS1	NR_169215.1		n.2697C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5-AS1	ENST00000310799.9	TSL:1	n.2726C>A		non_coding_transcript_exon	Exon 4 of 4
	KCNJ5-AS1	ENST00000524878.2	TSL:1	n.2712C>A		non_coding_transcript_exon	Exon 4 of 4
	KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.-11+8742G>T		intron	N/A	ENSP00000433295.1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12842 AN: 152030 Hom.: 1115 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0786

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 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) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0845 AC: 12849 AN: 152148 Hom.: 1113 Cov.: 33 AF XY: 0.0900 AC XY: 6698 AN XY: 74398

African (AFR) AF: 0.165 AC: 6839 AN: 41474

American (AMR) AF: 0.139 AC: 2123 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1248 AN: 5170

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4820

European-Finnish (FIN) AF: 0.0453 AC: 480 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 784 AN: 68020

Other (OTH) AF: 0.0806 AC: 170 AN: 2108

Alfa AF: 0.0414 Hom.: 717

Bravo AF: 0.0933

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		0.30
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: rs3740835; hg19: chr11-128770358;