dbSNP rs725937: SPARC:c.-13-949A>G (chr5-151677150-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003118.4(SPARC):c.-13-949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,096 control chromosomes in the GnomAD database, including 29,101 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 0.61 ( 29101 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

SPARC
NM_003118.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.568

Publications

9 publications found

Variant links:

Genes affected

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 links:

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

CLMAT3 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4 link	c.-13-949A>G	intron_variant	Intron 1 of 9	ENST00000231061.9	NP_003109.1	P09486
SPARC	NM_001309444.2 link	c.-13-949A>G	intron_variant	Intron 1 of 9		NP_001296373.1	P09486
SPARC	NM_001309443.2 link	c.-13-949A>G	intron_variant	Intron 1 of 9		NP_001296372.1	P09486
CLMAT3	NR_109873.1 link	n.103+103T>C	intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 link	c.-13-949A>G		intron_variant	Intron 1 of 9	1	NM_003118.4	ENSP00000231061.4		P09486

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93391

AN:

151976

Hom.:

29073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.605

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

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

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)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.615

AC:

93471

AN:

152094

Hom.:

29101

Cov.:

AF XY:

0.616

AC XY:

45832

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.694

AC:

28790

AN:

41494

American (AMR)

AF:

0.630

AC:

9632

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1959

AN:

3470

East Asian (EAS)

AF:

0.454

AC:

2350

AN:

5176

South Asian (SAS)

AF:

0.488

AC:

2352

AN:

4820

European-Finnish (FIN)

AF:

0.640

AC:

6757

AN:

10566

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39581

AN:

67966

Other (OTH)

AF:

0.609

AC:

1287

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1867

3733

5600

7466

9333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.590

Hom.:

34416

Bravo

AF:

0.618

Asia WGS

AF:

0.523

AC:

1820

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.4

(source)

DANN

Benign

0.73

PhyloP100

0.57

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

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

rs725937

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