rs12795437

Variant names:

• chr11-128860981-G-C
• rs12795437
• NM_153766.3:c.-192+6192C>G

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+6192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 152,272 control chromosomes in the GnomAD database, including 394 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 0.061 (394 hom., cov: 33)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.088 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.-192+6192C>G		intron	N/A	NP_722450.1
	KCNJ1	NM_153765.3		c.30+5542C>G		intron	N/A	NP_722449.3
	KCNJ1	NM_153764.3		c.-22+6192C>G		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.-192+6192C>G		intron	N/A	ENSP00000376434.1
	KCNJ1	ENST00000324036.7	TSL:1	c.-192+5542C>G		intron	N/A	ENSP00000316233.3
	KCNJ1	ENST00000392665.6	TSL:1	c.-22+6192C>G		intron	N/A	ENSP00000376433.2

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9330 AN: 152154 Hom.: 393 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0981

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0613 AC: 9332 AN: 152272 Hom.: 394 Cov.: 33 AF XY: 0.0615 AC XY: 4582 AN XY: 74456

African (AFR) AF: 0.0176 AC: 731 AN: 41554

American (AMR) AF: 0.0920 AC: 1406 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0981 AC: 340 AN: 3466

East Asian (EAS) AF: 0.0611 AC: 317 AN: 5192

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4824

European-Finnish (FIN) AF: 0.0901 AC: 955 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5207 AN: 68030

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0627 Hom.: 31

Bravo AF: 0.0611

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.79
PhyloP100		-0.18
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: rs12795437; hg19: chr11-128730876;