1-150624785-G-A

Variant names:

• chr1-150624785-G-A
• rs1971378
• ENST00000356527.9:c.*853C>T

Variant summary

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

The NM_207043.2(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 NM_207043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 11 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207043.2. 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
	ENSA	NM_004436.4	MANE Select	c.350+857C>T		intron	N/A	NP_004427.1	O43768-1
	ENSA	NM_207043.2		c.*853C>T		3_prime_UTR	Exon 4 of 4	NP_996926.1	O43768-9
	ENSA	NM_207044.2		c.*853C>T		3_prime_UTR	Exon 3 of 3	NP_996927.1	O43768-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSA	ENST00000356527.9	TSL:1	c.*853C>T		3_prime_UTR	Exon 3 of 3	ENSP00000348921.5	A6NMQ3
	ENSA	ENST00000271690.12	TSL:1	c.*853C>T		3_prime_UTR	Exon 3 of 3	ENSP00000271690.7	O43768-2
	ENSA	ENST00000369014.10	TSL:1 MANE Select	c.350+857C>T		intron	N/A	ENSP00000358010.6	O43768-1

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

African (AFR) AF: 0.157 AC: 2483 AN: 15780

American (AMR) AF: 0.383 AC: 376 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1938 AN: 5150

East Asian (EAS) AF: 0.396 AC: 1436 AN: 3630

South Asian (SAS) AF: 0.330 AC: 5429 AN: 16448

European-Finnish (FIN) AF: 0.577 AC: 158 AN: 274

Middle Eastern (MID) AF: 0.419 AC: 679 AN: 1620

European-Non Finnish (NFE) AF: 0.554 AC: 421778 AN: 761156

Other (OTH) AF: 0.490 AC: 13369 AN: 27268

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

African (AFR) AF: 0.188 AC: 7782 AN: 41468

American (AMR) AF: 0.403 AC: 6157 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2057 AN: 5178

South Asian (SAS) AF: 0.324 AC: 1566 AN: 4826

European-Finnish (FIN) AF: 0.562 AC: 5918 AN: 10536

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36988 AN: 67948

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.422 Hom.: 3462

Bravo AF: 0.396

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.6
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: rs1971378; hg19: chr1-150597261;