dbSNP rs4958281: CLMAT3:n.1100C>T (chr5-151687037-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000510576.6(CLMAT3):n.1100C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 153,708 control chromosomes in the GnomAD database, including 190 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 0.042 ( 189 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1 hom. )

Consequence

CLMAT3
ENST00000510576.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Publications

4 publications found

Variant links:

Genes affected

CLMAT3 (HGNC:52287): (colorectal liver metastasis associated transcript 3)

CLMAT3 links:

SPARC (HGNC:11219): (secreted protein acidic and cysteine rich) This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2015]

SPARC Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 17
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
osteogenesis imperfecta type 4
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPARC 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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLMAT3	NR_109873.1 link	n.1100C>T	non_coding_transcript_exon_variant	Exon 5 of 5
SPARC	NM_003118.4 link	c.-186G>A	upstream_gene_variant		ENST00000231061.9	NP_003109.1	P09486
SPARC	NM_001309444.2 link	c.-186G>A	upstream_gene_variant			NP_001296373.1	P09486
SPARC	NM_001309443.2 link	c.-186G>A	upstream_gene_variant			NP_001296372.1	P09486

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 link	c.-186G>A		upstream_gene_variant		1	NM_003118.4	ENSP00000231061.4		P09486

Frequencies

GnomAD3 genomes

AF:

0.0422

AC:

6415

AN:

152136

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.0421

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0522

GnomAD4 exome

AF:

0.0509

AC:

AN:

1454

Hom.:

Cov.:

AF XY:

0.0535

AC XY:

AN XY:

972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.111

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AF:

0.0563

AC:

AN:

284

Middle Eastern (MID)

AF:

0.111

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0461

AC:

AN:

868

Other (OTH)

AF:

0.0370

AC:

AN:

162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0422

AC:

6419

AN:

152254

Hom.:

189

Cov.:

AF XY:

0.0440

AC XY:

3277

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0111

AC:

461

AN:

41548

American (AMR)

AF:

0.103

AC:

1580

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3472

East Asian (EAS)

AF:

0.0431

AC:

223

AN:

5178

South Asian (SAS)

AF:

0.0420

AC:

202

AN:

4814

European-Finnish (FIN)

AF:

0.0503

AC:

534

AN:

10624

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0460

AC:

3130

AN:

68002

Other (OTH)

AF:

0.0511

AC:

108

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

315

630

946

1261

1576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0443

Hom.:

269

Bravo

AF:

0.0469

Asia WGS

AF:

0.0460

AC:

161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

(source)

DANN

Benign

0.72

PhyloP100

-1.6

PromoterAI

-0.18

Neutral

(source)

Mutation Taster

=300/0

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

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rs4958281

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