1-150609962-C-T

Variant names:

• chr1-150609962-C-T
• rs1355637
• ENST00000369016.8:c.399-8683G>A

Variant summary

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

The ENST00000369016.8(ENSA):​c.399-8683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,164 control chromosomes in the GnomAD database, including 1,602 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 0.13 (1602 hom., cov: 32)
• Consequence: ENSA ENST00000369016.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

ENSA (HGNC:3360): (endosulfine alpha) The protein encoded by this gene belongs to a highly conserved cAMP-regulated phosphoprotein (ARPP) family. This protein was identified as an endogenous ligand for the sulfonylurea receptor, ABCC8/SUR1. ABCC8 is the regulatory subunit of the ATP-sensitive potassium (KATP) channel, which is located on the plasma membrane of pancreatic beta cells and plays a key role in the control of insulin release from pancreatic beta cells. This protein is thought to be an endogenous regulator of KATP channels. In vitro studies have demonstrated that this protein modulates insulin secretion through the interaction with KATP channel, and this gene has been proposed as a candidate gene for type 2 diabetes. At least eight alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 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
ENSA	ENST00000369016.8	c.399-8683G>A		intron_variant	Intron 4 of 4	5		ENSP00000358012.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19232 AN: 152046 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.126 AC: 19225 AN: 152164 Hom.: 1602 Cov.: 32 AF XY: 0.124 AC XY: 9209 AN XY: 74388

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.0463

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.130

Alfa AF: 0.156 Hom.: 1297

Bravo AF: 0.120

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1355637; hg19: chr1-150582438;