rs12795437

chr11-128860981-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC107984409 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ1	NM_153766.3	c.-192+6192C>G		intron_variant		ENST00000392666.6
LOC107984409	XR_001748442.2	n.59-2916G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-192+6192C>G		intron_variant		1	NM_153766.3	P1

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

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.0981

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.0738

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.2
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs12795437; hg19: chr11-128730876;