11-128839052-T-A

Variant summary

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

The NM_153766.3(KCNJ1):c.*73A>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 0.161 in 1,397,342 control chromosomes in the GnomAD database, including 19,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2049 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17477 hom.)
• Consequence: KCNJ1 NM_153766.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0890

Genes affected

KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) 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. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-128839052-T-A is Benign according to our data. Variant chr11-128839052-T-A is described in ClinVar as [Benign]. Clinvar id is 303567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128839052-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ1	NM_153766.3	c.*73A>T		3_prime_UTR_variant	3/3	ENST00000392666.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ1	ENST00000392666.6	c.*73A>T		3_prime_UTR_variant	3/3	1	NM_153766.3	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24464 AN: 152062 Hom.: 2041 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.161 AC: 199941 AN: 1245162 Hom.: 17477 Cov.: 17 AF XY: 0.165 AC XY: 103901 AN XY: 628520

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0875

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0978

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.161 AC: 24492 AN: 152180 Hom.: 2049 Cov.: 32 AF XY: 0.163 AC XY: 12161 AN XY: 74388

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.149

Alfa AF: 0.153 Hom.: 201

Bravo AF: 0.153

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Antenatal Bartter syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.68
Dann	Benign	0.50

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: rs1231254; hg19: chr11-128708947;