dbSNP rs2304051: SPARC:c.120+42T>C (chr5-151674570-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003118.4(SPARC):c.120+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 1,591,912 control chromosomes in the GnomAD database, including 11,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4098 hom., cov: 32)

Exomes 𝑓: 0.086 ( 7856 hom. )

Consequence

SPARC
NM_003118.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.57

Publications

6 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, Ambry Genetics, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae)
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-151674570-A-G is Benign according to our data. Variant chr5-151674570-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPARC	NM_003118.4	MANE Select	c.120+42T>C	intron	N/A	NP_003109.1	P09486
SPARC	NM_001309444.2		c.120+42T>C	intron	N/A	NP_001296373.1
SPARC	NM_001309443.2		c.117+42T>C	intron	N/A	NP_001296372.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPARC	ENST00000231061.9	TSL:1 MANE Select	c.120+42T>C	intron	N/A	ENSP00000231061.4	P09486
SPARC	ENST00000896427.1		c.120+42T>C	intron	N/A	ENSP00000566486.1
SPARC	ENST00000896428.1		c.120+42T>C	intron	N/A	ENSP00000566487.1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26176

AN:

151964

Hom.:

4077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0889

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0877

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0713

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.101

AC:

25236

AN:

249652

AF XY:

0.0981

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.0525

Gnomad ASJ exome

AF:

0.0817

Gnomad EAS exome

AF:

0.0660

Gnomad FIN exome

AF:

0.0807

Gnomad NFE exome

AF:

0.0712

Gnomad OTH exome

AF:

0.0777

GnomAD4 exome

AF:

0.0857

AC:

123408

AN:

1439830

Hom.:

7856

Cov.:

AF XY:

0.0868

AC XY:

62319

AN XY:

717820

show subpopulations

African (AFR)

AF:

0.438

AC:

14375

AN:

32816

American (AMR)

AF:

0.0564

AC:

2506

AN:

44422

Ashkenazi Jewish (ASJ)

AF:

0.0790

AC:

2047

AN:

25898

East Asian (EAS)

AF:

0.0743

AC:

2943

AN:

39600

South Asian (SAS)

AF:

0.138

AC:

11781

AN:

85630

European-Finnish (FIN)

AF:

0.0798

AC:

4255

AN:

53338

Middle Eastern (MID)

AF:

0.106

AC:

604

AN:

5718

European-Non Finnish (NFE)

AF:

0.0723

AC:

79005

AN:

1092728

Other (OTH)

AF:

0.0987

AC:

5892

AN:

59680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4776

9553

14329

19106

23882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3180

6360

9540

12720

15900

<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:

26238

AN:

152082

Hom.:

4098

Cov.:

AF XY:

0.171

AC XY:

12703

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.420

AC:

17407

AN:

41404

American (AMR)

AF:

0.0887

AC:

1356

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

310

AN:

3470

East Asian (EAS)

AF:

0.0650

AC:

337

AN:

5184

South Asian (SAS)

AF:

0.139

AC:

668

AN:

4816

European-Finnish (FIN)

AF:

0.0877

AC:

929

AN:

10592

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0713

AC:

4850

AN:

68010

Other (OTH)

AF:

0.153

AC:

324

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

895

1790

2685

3580

4475

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:

0.0640

Hom.:

146

Bravo

AF:

0.183

Asia WGS

AF:

0.114

AC:

400

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Osteogenesis imperfecta type 17 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.25

(source)

DANN

Benign

0.41

PhyloP100

-1.6

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

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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