11-128917535-G-T

Position:

• chr11-128917535-G-T

Variant summary

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

The NM_000890.5(KCNJ5):​c.*804G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,168 control chromosomes in the GnomAD database, including 41,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41963 hom., cov: 34)
  • Exomes 𝑓: 0.72 (46 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ5 NM_000890.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.163

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-128917535-G-T is Benign according to our data. Variant chr11-128917535-G-T is described in ClinVar as [Benign]. Clinvar id is 303649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.*804G>T		3_prime_UTR_variant	3/3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.*804G>T		3_prime_UTR_variant	4/4		NP_001341098.1
KCNJ5	XM_011542810.4	c.*804G>T		3_prime_UTR_variant	3/3		XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.*804G>T		3_prime_UTR_variant	3/3	1	NM_000890.5	ENSP00000433295.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112674 AN: 152050 Hom.: 41932 Cov.: 34

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.773

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.719 AC: 128 AN: 178 Hom.: 46 Cov.: 0 AF XY: 0.714 AC XY: 90 AN XY: 126

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.741 AC: 112764 AN: 152168 Hom.: 41963 Cov.: 34 AF XY: 0.741 AC XY: 55138 AN XY: 74390

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.774

Alfa AF: 0.714 Hom.: 6307

Bravo AF: 0.745

Asia WGS AF: 0.746 AC: 2588 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	May 12, 2021	- -

Familial hyperaldosteronism type III Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.76

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: rs2604204; hg19: chr11-128787430;