11-22821609-A-T

Variant names:

• chr11-22821609-A-T
• rs712022
• NM_148893.3:c.*1510T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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]

ACMG classification

Verdict is Benign. Variant got -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	c.*1510T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000354193.5	NP_683691.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81342 AN: 151908 Hom.: 22307 Cov.: 32

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.536 AC: 81417 AN: 152026 Hom.: 22322 Cov.: 32 AF XY: 0.531 AC XY: 39488 AN XY: 74300

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.522

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
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs712022; hg19: chr11-22843155;