rs2509585

Positions:

• chr11-128865501-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153766.3(KCNJ1):​c.-192+1672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,198 control chromosomes in the GnomAD database, including 1,109 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 0.11 (1109 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.-192+1672C>T		intron_variant		ENST00000392666.6	NP_722450.1
LOC107984409	XR_001748442.2	n.173-1249G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-192+1672C>T		intron_variant		1	NM_153766.3	ENSP00000376434	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17056 AN: 152080 Hom.: 1106 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0967

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17064 AN: 152198 Hom.: 1109 Cov.: 32 AF XY: 0.114 AC XY: 8478 AN XY: 74412

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0967

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.117

Alfa AF: 0.142 Hom.: 756

Bravo AF: 0.103

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.76

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: rs2509585; hg19: chr11-128735396;