11-128900463-G-T

Position:

• chr11-128900463-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000890.5(KCNJ5):​c.-11+8742G>T variant causes a intron 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 NM_000890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

Genes affected

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.-11+8742G>T		intron_variant		ENST00000529694.6	NP_000881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.-11+8742G>T		intron_variant		1	NM_000890.5	ENSP00000433295.1
KCNJ5	ENST00000338350.4	c.-100+8742G>T		intron_variant		1		ENSP00000339960.4
KCNJ5-AS1	ENST00000310799.9	n.2726C>A		non_coding_transcript_exon_variant	4/4	1
KCNJ5-AS1	ENST00000524878.2	n.2712C>A		non_coding_transcript_exon_variant	4/4	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

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.0806

Alfa AF: 0.0221 Hom.: 157

Bravo AF: 0.0933

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.67

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: rs3740835; hg19: chr11-128770358;