rs2855800

Variant names:

• chr11-128861060-A-C
• rs2855800
• NM_153766.3:c.-192+6113T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-128861060-A-C
• chr11-128861060-A-G
• chr11-128861060-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.-192+6113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,156 control chromosomes in the GnomAD database, including 5,958 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 0.27 (5958 hom., cov: 33)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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

LOC107984409 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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+6113T>G		intron	N/A	NP_722450.1
	KCNJ1	NM_153765.3		c.30+5463T>G		intron	N/A	NP_722449.3
	KCNJ1	NM_153764.3		c.-22+6113T>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+6113T>G		intron	N/A	ENSP00000376434.1
	KCNJ1	ENST00000324036.7	TSL:1	c.-192+5463T>G		intron	N/A	ENSP00000316233.3
	KCNJ1	ENST00000392665.6	TSL:1	c.-22+6113T>G		intron	N/A	ENSP00000376433.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41748 AN: 152038 Hom.: 5941 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.275 AC: 41824 AN: 152156 Hom.: 5958 Cov.: 33 AF XY: 0.273 AC XY: 20300 AN XY: 74384

African (AFR) AF: 0.325 AC: 13488 AN: 41492

American (AMR) AF: 0.242 AC: 3703 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3470

East Asian (EAS) AF: 0.149 AC: 775 AN: 5190

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2835 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17719 AN: 67970

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.249 Hom.: 2479

Bravo AF: 0.275

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.49
PhyloP100		-1.3
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: rs2855800; hg19: chr11-128730955;