rs2217332

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014685.4(HERPUD1):c.149G>A(p.Arg50His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,607,832 control chromosomes in the GnomAD database, including 17,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1582 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15542 hom. )

Consequence

HERPUD1
NM_014685.4 missense, splice_region

Scores

Splicing: ADA: 0.0001747

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

57 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0019485354).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERPUD1	NM_014685.4 link	c.149G>A	p.Arg50His	missense_variant, splice_region_variant	Exon 2 of 8	ENST00000439977.7	NP_055500.1	Q15011-1Q53FP9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERPUD1	ENST00000439977.7 link	c.149G>A	p.Arg50His	missense_variant, splice_region_variant	Exon 2 of 8	1	NM_014685.4	ENSP00000409555.2		Q15011-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21382

AN:

152056

Hom.:

1581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0765

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.149

GnomAD2 exomes

AF:

0.150

AC:

37626

AN:

251376

AF XY:

0.153

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0761

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.143

AC:

208523

AN:

1455658

Hom.:

15542

Cov.:

AF XY:

0.145

AC XY:

105312

AN XY:

724622

show subpopulations

African (AFR)

AF:

0.114

AC:

3821

AN:

33374

American (AMR)

AF:

0.161

AC:

7183

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4758

AN:

26090

East Asian (EAS)

AF:

0.0766

AC:

3040

AN:

39666

South Asian (SAS)

AF:

0.206

AC:

17697

AN:

86072

European-Finnish (FIN)

AF:

0.142

AC:

7579

AN:

53406

Middle Eastern (MID)

AF:

0.196

AC:

1127

AN:

5750

European-Non Finnish (NFE)

AF:

0.140

AC:

154368

AN:

1106376

Other (OTH)

AF:

0.149

AC:

8950

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

8018

16037

24055

32074

40092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5554

11108

16662

22216

27770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.141

AC:

21392

AN:

152174

Hom.:

1582

Cov.:

AF XY:

0.142

AC XY:

10561

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.121

AC:

5035

AN:

41504

American (AMR)

AF:

0.174

AC:

2657

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

636

AN:

3472

East Asian (EAS)

AF:

0.0767

AC:

398

AN:

5188

South Asian (SAS)

AF:

0.201

AC:

971

AN:

4820

European-Finnish (FIN)

AF:

0.134

AC:

1417

AN:

10574

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9721

AN:

68010

Other (OTH)

AF:

0.148

AC:

313

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

909

1818

2728

3637

4546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.144

Hom.:

8055

Bravo

AF:

0.141

TwinsUK

AF:

0.144

AC:

534

ALSPAC

AF:

0.143

AC:

552

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.156

AC:

1340

ExAC

AF:

0.150

AC:

18195

Asia WGS

AF:

0.150

AC:

521

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.13

T;.;.;.;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.45

T;T;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;L;.;.

PhyloP100

0.10

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.83

N;N;N;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.25

T;T;T;T;D;D

Sift4G

Benign

0.58

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;.;.;.

Vest4

0.055

MPC

0.25

ClinPred

0.0015

GERP RS

3.1

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.3

Varity_R

0.050

gMVP

0.41

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.010

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over