rs3016774

Variant names:

• chr11-128865771-T-C
• rs3016774
• NM_153766.3:c.-192+1402A>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+1402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,078 control chromosomes in the GnomAD database, including 2,599 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 0.18 (2599 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.-192+1402A>G		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+1402A>G		intron_variant	Intron 1 of 2	1	NM_153766.3	ENSP00000376434.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27558 AN: 151960 Hom.: 2586 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.182 AC: 27619 AN: 152078 Hom.: 2599 Cov.: 32 AF XY: 0.182 AC XY: 13509 AN XY: 74362

African (AFR) AF: 0.198 AC: 8226 AN: 41454

American (AMR) AF: 0.134 AC: 2050 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.121 AC: 628 AN: 5184

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12322 AN: 67984

Other (OTH) AF: 0.177 AC: 374 AN: 2110

Alfa AF: 0.187 Hom.: 1578

Bravo AF: 0.177

Asia WGS AF: 0.205 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		0.43
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: rs3016774; hg19: chr11-128735666;