ENST00000938506.1:c.-76+208A>G

Variant names:

• chr16-56931795-A-G
• rs3764263
• ENST00000938506.1:c.-76+208A>G

Variant summary

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

The ENST00000938506.1(HERPUD1):​c.-76+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,090 control chromosomes in the GnomAD database, including 31,308 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 0.63 (31308 hom., cov: 32)
• Consequence: HERPUD1 ENST00000938506.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 10 publications found

Genes affected

HERPUD1 (HGNC:13744): (homocysteine inducible ER protein with ubiquitin like domain 1) The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jan 2013]

ENSG00000307937 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000938506.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD1	ENST00000938506.1		c.-76+208A>G		intron	N/A	ENSP00000608565.1
	HERPUD1	ENST00000951120.1		c.-76+208A>G		intron	N/A	ENSP00000621179.1
	ENSG00000307937	ENST00000829929.1		n.691-74T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95138 AN: 151972 Hom.: 31273 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95212 AN: 152090 Hom.: 31308 Cov.: 32 AF XY: 0.624 AC XY: 46411 AN XY: 74352

African (AFR) AF: 0.833 AC: 34619 AN: 41540

American (AMR) AF: 0.558 AC: 8529 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1981 AN: 3466

East Asian (EAS) AF: 0.310 AC: 1594 AN: 5146

South Asian (SAS) AF: 0.496 AC: 2394 AN: 4830

European-Finnish (FIN) AF: 0.623 AC: 6599 AN: 10586

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37484 AN: 67918

Other (OTH) AF: 0.621 AC: 1311 AN: 2112

Alfa AF: 0.573 Hom.: 41262

Bravo AF: 0.629

Asia WGS AF: 0.470 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.24
DANN	Benign	0.65
PhyloP100		-1.4
PromoterAI		0.0032	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3764263; hg19: chr16-56965707;