rs2846679

Variant names:

• chr11-128859649-G-A
• rs2846679
• NM_153766.3:c.-192+7524C>T

Variant summary

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

The NM_153766.3(KCNJ1):​c.-192+7524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,138 control chromosomes in the GnomAD database, including 1,210 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 0.12 (1210 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 5 publications found

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]

KCNJ1 Gene-Disease associations (from GenCC):

• Bartter disease type 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984409 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.-192+7524C>T		intron_variant	Intron 1 of 2	ENST00000392666.6	NP_722450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-192+7524C>T		intron_variant	Intron 1 of 2	1	NM_153766.3	ENSP00000376434.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17724 AN: 152020 Hom.: 1208 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0993

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17732 AN: 152138 Hom.: 1210 Cov.: 32 AF XY: 0.120 AC XY: 8913 AN XY: 74378

African (AFR) AF: 0.0500 AC: 2077 AN: 41548

American (AMR) AF: 0.0873 AC: 1334 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 344 AN: 3464

East Asian (EAS) AF: 0.0890 AC: 460 AN: 5168

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4814

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10588

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9929 AN: 67954

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.101 Hom.: 369

Bravo AF: 0.105

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		1.4
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: rs2846679; hg19: chr11-128729544;