rs768919537

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_152415.3(VPS37A):c.125+49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 0 hom., cov: 0)

Exomes 𝑓: 0.063 ( 13 hom. )

Failed GnomAD Quality Control

Consequence

VPS37A
NM_152415.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00900

Publications

0 publications found

Variant links:

Genes affected

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

VPS37A links:

CNOT7 (HGNC:14101): (CCR4-NOT transcription complex subunit 7) The protein encoded by this gene binds to an anti-proliferative protein, B-cell translocation protein 1, which negatively regulates cell proliferation. Binding of the two proteins, which is driven by phosphorylation of the anti-proliferative protein, causes signaling events in cell division that lead to changes in cell proliferation associated with cell-cell contact. The encoded protein downregulates the innate immune response and therefore provides a therapeutic target for enhancing its antimicrobial activity against foreign agents. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Apr 2016]

CNOT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 8-17247418-C-G is Benign according to our data. Variant chr8-17247418-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1194269.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS37A	NM_152415.3	MANE Select	c.125+49C>G	intron	N/A	NP_689628.2	Q8NEZ2-1
VPS37A	NM_001363173.2		c.125+49C>G	intron	N/A	NP_001350102.1	Q8NEZ2-1
VPS37A	NM_001363167.1		c.125+49C>G	intron	N/A	NP_001350096.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS37A	ENST00000324849.9	TSL:1 MANE Select	c.125+49C>G	intron	N/A	ENSP00000318629.4	Q8NEZ2-1
VPS37A	ENST00000521829.5	TSL:1	c.125+49C>G	intron	N/A	ENSP00000429680.1	Q8NEZ2-2
VPS37A	ENST00000967262.1		c.125+49C>G	intron	N/A	ENSP00000637321.1

Frequencies

GnomAD3 genomes

AF:

0.00817

AC:

227

AN:

27774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00998

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00698

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00535

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00843

Gnomad OTH

AF:

0.0159

GnomAD2 exomes

AF:

0.0324

AC:

678

AN:

20932

AF XY:

0.0278

show subpopulations

Gnomad AFR exome

AF:

0.0462

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.0485

Gnomad FIN exome

AF:

0.0443

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0418

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0627

AC:

6582

AN:

104922

Hom.:

Cov.:

AF XY:

0.0670

AC XY:

3727

AN XY:

55594

show subpopulations

African (AFR)

AF:

0.0432

AC:

AN:

1806

American (AMR)

AF:

0.160

AC:

365

AN:

2286

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

108

AN:

2608

East Asian (EAS)

AF:

0.0423

AC:

AN:

2224

South Asian (SAS)

AF:

0.107

AC:

1456

AN:

13550

European-Finnish (FIN)

AF:

0.0455

AC:

345

AN:

7586

Middle Eastern (MID)

AF:

0.0804

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0541

AC:

3808

AN:

70342

Other (OTH)

AF:

0.0720

AC:

305

AN:

4234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

179

358

538

717

896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00816

AC:

227

AN:

27812

Hom.:

Cov.:

AF XY:

0.00820

AC XY:

113

AN XY:

13780

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00993

AC:

AN:

6644

American (AMR)

AF:

0.00694

AC:

AN:

2160

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

714

East Asian (EAS)

AF:

0.00

AC:

AN:

1434

South Asian (SAS)

AF:

0.0114

AC:

AN:

700

European-Finnish (FIN)

AF:

0.00535

AC:

AN:

1496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00843

AC:

118

AN:

13998

Other (OTH)

AF:

0.0155

AC:

AN:

322

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.306

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000184

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.6

(source)

DANN

Benign

0.74

PhyloP100

-0.0090

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over