NM_001897.5:c.914C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001897.5(CSPG4):c.914C>T(p.Thr305Met) variant causes a missense change. The variant allele was found at a frequency of 0.00903 in 142,802 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CSPG4
NM_001897.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.15

Publications

7 publications found

Variant links:

Genes affected

CSPG4 (HGNC:2466): (chondroitin sulfate proteoglycan 4) A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]

CSPG4 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CSPG4 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=0.003302157).

BP6

Variant 15-75690151-G-A is Benign according to our data. Variant chr15-75690151-G-A is described in ClinVar as Benign. ClinVar VariationId is 402567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG4	NM_001897.5 link	c.914C>T	p.Thr305Met	missense_variant	Exon 3 of 10	ENST00000308508.5	NP_001888.2	Q6UVK1
CSPG4	XM_047432196.1 link	c.-149C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 10		XP_047288152.1
CSPG4	XM_047432196.1 link	c.-149C>T		5_prime_UTR_variant	Exon 3 of 10		XP_047288152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG4	ENST00000308508.5 link	c.914C>T	p.Thr305Met	missense_variant	Exon 3 of 10	1	NM_001897.5	ENSP00000312506.5		Q6UVK1

Frequencies

GnomAD3 genomes

AF:

0.00900

AC:

1284

AN:

142732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00293

Gnomad EAS

AF:

0.000775

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000663

Gnomad MID

AF:

0.00685

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00914

GnomAD2 exomes

AF:

0.00786

AC:

1926

AN:

244940

AF XY:

0.00666

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.00394

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00502

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00477

AC:

6847

AN:

1435236

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

3320

AN XY:

714496

show subpopulations

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

African (AFR)

AF:

0.0634

AC:

1722

AN:

27180

American (AMR)

AF:

0.00382

AC:

167

AN:

43700

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

25686

East Asian (EAS)

AF:

0.000462

AC:

AN:

38948

South Asian (SAS)

AF:

0.00116

AC:

AN:

85570

European-Finnish (FIN)

AF:

0.00145

AC:

AN:

52256

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00393

AC:

4313

AN:

1097686

Other (OTH)

AF:

0.00549

AC:

322

AN:

58686

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.250

Heterozygous variant carriers

959

1918

2876

3835

4794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

228

456

684

912

1140

<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:

0.00903

AC:

1290

AN:

142802

Hom.:

Cov.:

AF XY:

0.00911

AC XY:

637

AN XY:

69902

show subpopulations

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

African (AFR)

AF:

0.0313

AC:

1065

AN:

34032

American (AMR)

AF:

0.00398

AC:

AN:

14810

Ashkenazi Jewish (ASJ)

AF:

0.00293

AC:

AN:

3418

East Asian (EAS)

AF:

0.000777

AC:

AN:

5148

South Asian (SAS)

AF:

0.00104

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.000663

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00741

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00179

AC:

120

AN:

66874

Other (OTH)

AF:

0.00904

AC:

AN:

1992

⚠️ 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: 0.253

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.0138

Hom.:

ExAC

AF:

0.0206

AC:

2502

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0033

MetaSVM

Uncertain

-0.013

MutationAssessor

Benign

1.9

PhyloP100

5.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.50

Sift

Uncertain

0.014

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.24

MPC

0.91

ClinPred

0.015

GERP RS

5.3

Varity_R

0.079

gMVP

0.62

Mutation Taster

=74/26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over