rs7517

Variant names:

• chr1-150623935-C-A
• rs7517
• ENST00000356527.9:c.*1703G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356527.9(ENSA):​c.*1703G>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 0.0962 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 ENST00000356527.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 20 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356527.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSA	NM_004436.4	MANE Select	c.351-1076G>T		intron	N/A	NP_004427.1
	ENSA	NM_207043.2		c.*1703G>T		3_prime_UTR	Exon 4 of 4	NP_996926.1
	ENSA	NM_207044.2		c.*1703G>T		3_prime_UTR	Exon 3 of 3	NP_996927.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSA	ENST00000356527.9	TSL:1	c.*1703G>T		3_prime_UTR	Exon 3 of 3	ENSP00000348921.5
	ENSA	ENST00000271690.12	TSL:1	c.*1703G>T		3_prime_UTR	Exon 3 of 3	ENSP00000271690.7
	ENSA	ENST00000369014.10	TSL:1 MANE Select	c.351-1076G>T		intron	N/A	ENSP00000358010.6

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

African (AFR) AF: 0.266 AC: 4206 AN: 15786

American (AMR) AF: 0.0965 AC: 95 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 795 AN: 5152

East Asian (EAS) AF: 0.185 AC: 673 AN: 3630

South Asian (SAS) AF: 0.114 AC: 1875 AN: 16460

European-Finnish (FIN) AF: 0.0747 AC: 23 AN: 308

Middle Eastern (MID) AF: 0.135 AC: 219 AN: 1622

European-Non Finnish (NFE) AF: 0.0818 AC: 62297 AN: 761904

Other (OTH) AF: 0.101 AC: 2757 AN: 27302

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

African (AFR) AF: 0.253 AC: 10496 AN: 41422

American (AMR) AF: 0.0938 AC: 1432 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.177 AC: 916 AN: 5170

South Asian (SAS) AF: 0.112 AC: 539 AN: 4810

European-Finnish (FIN) AF: 0.0960 AC: 1016 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6469 AN: 68010

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.105 Hom.: 1622

Bravo AF: 0.150

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.63
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7517; hg19: chr1-150596411;