1-150609962-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369016.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSA	ENST00000369016.8	TSL:5	c.399-8683G>A		intron	N/A	ENSP00000358012.4	Q5T5H1

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

African (AFR) AF: 0.0366 AC: 1519 AN: 41540

American (AMR) AF: 0.122 AC: 1857 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3472

East Asian (EAS) AF: 0.0180 AC: 93 AN: 5180

South Asian (SAS) AF: 0.0463 AC: 223 AN: 4816

European-Finnish (FIN) AF: 0.173 AC: 1827 AN: 10570

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12792 AN: 67992

Other (OTH) AF: 0.130 AC: 274 AN: 2112

Alfa AF: 0.152 Hom.: 1985

Bravo AF: 0.120

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.81
PhyloP100		-0.071
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1355637; hg19: chr1-150582438;