Genetic Variant SVIP:c.*1510T>A (chr11-22821609-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_148893.3(SVIP):c.*1510T>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 0.536 in 152,026 control chromosomes in the GnomAD database, including 22,322 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 0.54 ( 22322 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

SVIP
NM_148893.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.195

Publications

16 publications found

Variant links:

Genes affected

SVIP (HGNC:25238): (small VCP interacting protein) Endoplasmic reticulum-associated degradation (ERAD) is the pathway by which misfolded proteins in the endoplasmic reticulum are targeted to the proteasome for degradation. Multiple specialized proteins interact with one another during ERAD to complete this process. The protein encoded by this gene is an inhibitor of ERAD, functioning to disrupt the interaction of these protein components. This downregulation of ERAD may be needed to protect the cell from overactive protein degradation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

SVIP links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIP	NM_148893.3 link	c.*1510T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000354193.5	NP_683691.1	Q8NHG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIP	ENST00000354193.5 link	c.*1510T>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_148893.3	ENSP00000346130.4		Q8NHG7
SVIP	ENST00000525670.5 link	n.169-1273T>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81342

AN:

151908

Hom.:

22307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.520

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.536

AC:

81417

AN:

152026

Hom.:

22322

Cov.:

AF XY:

0.531

AC XY:

39488

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.513

AC:

21268

AN:

41446

American (AMR)

AF:

0.507

AC:

7750

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2015

AN:

3468

East Asian (EAS)

AF:

0.230

AC:

1188

AN:

5176

South Asian (SAS)

AF:

0.387

AC:

1867

AN:

4828

European-Finnish (FIN)

AF:

0.628

AC:

6619

AN:

10548

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38978

AN:

67966

Other (OTH)

AF:

0.522

AC:

1104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1898

3796

5694

7592

9490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.541

Hom.:

11505

Bravo

AF:

0.530

Asia WGS

AF:

0.345

AC:

1201

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.69

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over