rs675759

chr11-128838080-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153766.3(KCNJ1):c.*1045C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,592 control chromosomes in the GnomAD database, including 2,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2009 hom., cov: 32)
  • Exomes 𝑓: 0.20 (10 hom.)
• Consequence: KCNJ1 NM_153766.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.700

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-128838080-G-C is Benign according to our data. Variant chr11-128838080-G-C is described in ClinVar as [Benign]. Clinvar id is 303553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ1	NM_153766.3	c.*1045C>G		3_prime_UTR_variant	3/3	ENST00000392666.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ1	ENST00000392666.6	c.*1045C>G		3_prime_UTR_variant	3/3	1	NM_153766.3	P1
KCNJ1	ENST00000392665.6	c.*1045C>G		3_prime_UTR_variant	2/2	1		P1
KCNJ1	ENST00000440599.6	c.*1045C>G		3_prime_UTR_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24282 AN: 152090 Hom.: 2004 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.202 AC: 78 AN: 386 Hom.: 10 Cov.: 0 AF XY: 0.196 AC XY: 44 AN XY: 224

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.160 AC: 24308 AN: 152206 Hom.: 2009 Cov.: 32 AF XY: 0.162 AC XY: 12073 AN XY: 74426

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.148

Alfa AF: 0.154 Hom.: 229

Bravo AF: 0.152

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Antenatal Bartter syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs675759; hg19: chr11-128707975;