Variant rs2518054 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014685.4(HERPUD1):c.*696G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 172,048 control chromosomes in the GnomAD database, including 1,415 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 0.11 ( 1170 hom., cov: 32)

Exomes 𝑓: 0.14 ( 245 hom. )

Consequence

HERPUD1
NM_014685.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Variant links:

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]

HERPUD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
HERPUD1	NM_014685.4 linkuse as main transcript	c.*696G>A	3_prime_UTR_variant	8/8	ENST00000439977.7	NP_055500.1
HERPUD1	NM_001010989.3 linkuse as main transcript	c.*696G>A	3_prime_UTR_variant	8/8		NP_001010989.1
HERPUD1	NM_001272103.2 linkuse as main transcript	c.*887G>A	3_prime_UTR_variant	8/8		NP_001259032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERPUD1	ENST00000439977.7 linkuse as main transcript	c.*696G>A		3_prime_UTR_variant	8/8	1	NM_014685.4	ENSP00000409555	P4	Q15011-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16069

AN:

152112

Hom.:

1161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.143

AC:

2838

AN:

19818

Hom.:

245

Cov.:

AF XY:

0.145

AC XY:

1351

AN XY:

9308

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.106

AC:

16074

AN:

152230

Hom.:

1170

Cov.:

AF XY:

0.110

AC XY:

8187

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.116

Hom.:

2000

Bravo

AF:

0.108

Asia WGS

AF:

0.214

AC:

742

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over