rs675482

Variant names:

• chr11-128856699-A-G
• rs675482
• NM_153766.3:c.-191-5809T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-128856699-A-G
• chr11-128856699-A-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.-191-5809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,964 control chromosomes in the GnomAD database, including 8,292 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 0.32 (8292 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153766.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	NM_153766.3	MANE Select	c.-191-5809T>C		intron	N/A	NP_722450.1
	KCNJ1	NM_153765.3		c.30+9824T>C		intron	N/A	NP_722449.3
	KCNJ1	NM_153764.3		c.-22+10474T>C		intron	N/A	NP_722448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	ENST00000392666.6	TSL:1 MANE Select	c.-191-5809T>C		intron	N/A	ENSP00000376434.1
	KCNJ1	ENST00000324036.7	TSL:1	c.-191-5809T>C		intron	N/A	ENSP00000316233.3
	KCNJ1	ENST00000392665.6	TSL:1	c.-22+10474T>C		intron	N/A	ENSP00000376433.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49305 AN: 151844 Hom.: 8280 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.325 AC: 49349 AN: 151964 Hom.: 8292 Cov.: 32 AF XY: 0.326 AC XY: 24248 AN XY: 74280

African (AFR) AF: 0.398 AC: 16481 AN: 41444

American (AMR) AF: 0.252 AC: 3850 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2153 AN: 5154

South Asian (SAS) AF: 0.386 AC: 1860 AN: 4814

European-Finnish (FIN) AF: 0.342 AC: 3612 AN: 10552

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19589 AN: 67928

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.302 Hom.: 29901

Bravo AF: 0.325

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.071
DANN	Benign	0.23
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: rs675482; hg19: chr11-128726594;