rs2304052

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003118.4(SPARC):c.66A>G(p.Glu22Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 1,613,444 control chromosomes in the GnomAD database, including 12,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4106 hom., cov: 32)

Exomes 𝑓: 0.086 ( 8017 hom. )

Consequence

SPARC
NM_003118.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0140

Publications

29 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 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-151674666-T-C is Benign according to our data. Variant chr5-151674666-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4 link	c.66A>G	p.Glu22Glu	synonymous_variant	Exon 3 of 10	ENST00000231061.9	NP_003109.1	P09486
SPARC	NM_001309444.2 link	c.66A>G	p.Glu22Glu	synonymous_variant	Exon 3 of 10		NP_001296373.1	P09486
SPARC	NM_001309443.2 link	c.63A>G	p.Glu21Glu	synonymous_variant	Exon 3 of 10		NP_001296372.1	P09486

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 link	c.66A>G	p.Glu22Glu	synonymous_variant	Exon 3 of 10	1	NM_003118.4	ENSP00000231061.4		P09486

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26219

AN:

152036

Hom.:

4085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0890

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.0649

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0881

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0713

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.101

AC:

25390

AN:

251106

AF XY:

0.0982

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.0816

Gnomad EAS exome

AF:

0.0660

Gnomad FIN exome

AF:

0.0811

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0773

GnomAD4 exome

AF:

0.0861

AC:

125767

AN:

1461290

Hom.:

8017

Cov.:

AF XY:

0.0871

AC XY:

63302

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.439

AC:

14685

AN:

33438

American (AMR)

AF:

0.0565

AC:

2526

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0791

AC:

2068

AN:

26128

East Asian (EAS)

AF:

0.0742

AC:

2947

AN:

39692

South Asian (SAS)

AF:

0.138

AC:

11893

AN:

86218

European-Finnish (FIN)

AF:

0.0800

AC:

4271

AN:

53406

Middle Eastern (MID)

AF:

0.105

AC:

608

AN:

5768

European-Non Finnish (NFE)

AF:

0.0727

AC:

80794

AN:

1111564

Other (OTH)

AF:

0.0990

AC:

5975

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

5483

10965

16448

21930

27413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3272

6544

9816

13088

16360

<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:

0.173

AC:

26281

AN:

152154

Hom.:

4106

Cov.:

AF XY:

0.171

AC XY:

12719

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.421

AC:

17441

AN:

41458

American (AMR)

AF:

0.0887

AC:

1358

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

311

AN:

3470

East Asian (EAS)

AF:

0.0645

AC:

333

AN:

5164

South Asian (SAS)

AF:

0.139

AC:

669

AN:

4820

European-Finnish (FIN)

AF:

0.0881

AC:

934

AN:

10598

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0713

AC:

4853

AN:

68020

Other (OTH)

AF:

0.154

AC:

325

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

930

1859

2789

3718

4648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.110

Hom.:

5257

Bravo

AF:

0.183

Asia WGS

AF:

0.114

AC:

400

AN:

3478

EpiCase

AF:

0.0747

EpiControl

AF:

0.0754

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Osteogenesis imperfecta type 17

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.014

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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