rs1971378

Positions:

• chr1-150624785-G-A
• chr1-150624785-G-T

Variant summary

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

The ENST00000356527.9(ENSA):​c.*853C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 984,308 control chromosomes in the GnomAD database, including 137,765 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 0.42 (15202 hom., cov: 32)
  • Exomes 𝑓: 0.54 (122563 hom.)
• Consequence: ENSA ENST00000356527.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENSA	NM_004436.4	c.350+857C>T		intron_variant		ENST00000369014.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENSA	ENST00000369014.10	c.350+857C>T		intron_variant		1	NM_004436.4	P4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63374 AN: 151882 Hom.: 15208 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.538 AC: 447646 AN: 832308 Hom.: 122563 Cov.: 31 AF XY: 0.537 AC XY: 206531 AN XY: 384368

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.417 AC: 63363 AN: 152000 Hom.: 15202 Cov.: 32 AF XY: 0.416 AC XY: 30881 AN XY: 74256

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.448

Alfa AF: 0.434 Hom.: 3086

Bravo AF: 0.396

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.63

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: rs1971378; hg19: chr1-150597261;