rs7517

Positions:

• chr1-150623935-C-A
• chr1-150623935-C-T

Variant summary

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

The ENST00000369014.10(ENSA):​c.351-1076G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 985,206 control chromosomes in the GnomAD database, including 5,615 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 0.14 (1996 hom., cov: 32)
  • Exomes 𝑓: 0.088 (3619 hom.)
• Consequence: ENSA ENST00000369014.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENSA	NM_004436.4	c.351-1076G>T		intron_variant		ENST00000369014.10	NP_004427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSA	ENST00000369014.10	c.351-1076G>T		intron_variant		1	NM_004436.4	ENSP00000358010	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21764 AN: 151940 Hom.: 1986 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0875 AC: 72940 AN: 833148 Hom.: 3619 Cov.: 30 AF XY: 0.0873 AC XY: 33583 AN XY: 384736

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.0965

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0747

Gnomad4 NFE exome AF: 0.0818

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.143 AC: 21816 AN: 152058 Hom.: 1996 Cov.: 32 AF XY: 0.142 AC XY: 10555 AN XY: 74336

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0951

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0988 Hom.: 980

Bravo AF: 0.150

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs7517; hg19: chr1-150596411;