rs1557765

Variant names:

• chr11-17382092-T-C
• rs1557765
• ENST00000682764.1:c.*50+4777A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-17382092-T-C
• chr11-17382092-T-G

Variant summary

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

The ENST00000682764.1(KCNJ11):​c.*50+4777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,212 control chromosomes in the GnomAD database, including 38,474 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 0.70 (38459 hom., cov: 33)
  • Exomes 𝑓: 0.65 (15 hom.)
• Consequence: KCNJ11 ENST00000682764.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

KCNJ11 (HGNC:6257): (potassium inwardly rectifying channel subfamily J member 11) 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. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

ENSG00000260196 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ11	ENST00000682764.1	c.*50+4777A>G		intron_variant	Intron 2 of 2			ENSP00000506780.1
ENSG00000260196	ENST00000568280.1	n.1444T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106151 AN: 152028 Hom.: 38411 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.684

GnomAD4 exome AF: 0.652 AC: 43 AN: 66 Hom.: 15 Cov.: 0 AF XY: 0.620 AC XY: 31 AN XY: 50

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.698 AC: 106260 AN: 152146 Hom.: 38459 Cov.: 33 AF XY: 0.693 AC XY: 51562 AN XY: 74384

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.683

Alfa AF: 0.645 Hom.: 18616

Bravo AF: 0.714

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1557765; hg19: chr11-17403639;