dbSNP rs1978707: SPARC:c.208+31C>T (chr5-151673098-G-A) – 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.208+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,533,806 control chromosomes in the GnomAD database, including 277,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32418 hom., cov: 33)

Exomes 𝑓: 0.59 ( 244776 hom. )

Consequence

SPARC
NM_003118.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0850

Publications

17 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=-0.79).

BP6

Variant 5-151673098-G-A is Benign according to our data. Variant chr5-151673098-G-A is described in ClinVar as Benign. ClinVar VariationId is 1278457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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.208+31C>T	intron	N/A	NP_003109.1	P09486
SPARC	NM_001309444.2		c.208+31C>T	intron	N/A	NP_001296373.1
SPARC	NM_001309443.2		c.205+31C>T	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.208+31C>T	intron	N/A	ENSP00000231061.4	P09486
SPARC	ENST00000896427.1		c.208+31C>T	intron	N/A	ENSP00000566486.1
SPARC	ENST00000896428.1		c.208+31C>T	intron	N/A	ENSP00000566487.1

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98276

AN:

152022

Hom.:

32374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.633

GnomAD2 exomes

AF:

0.605

AC:

151939

AN:

251256

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.783

Gnomad AMR exome

AF:

0.663

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.593

AC:

818919

AN:

1381664

Hom.:

244776

Cov.:

AF XY:

0.589

AC XY:

408102

AN XY:

692384

show subpopulations

African (AFR)

AF:

0.788

AC:

25136

AN:

31886

American (AMR)

AF:

0.657

AC:

29347

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

15040

AN:

25662

East Asian (EAS)

AF:

0.534

AC:

20993

AN:

39288

South Asian (SAS)

AF:

0.543

AC:

45924

AN:

84618

European-Finnish (FIN)

AF:

0.647

AC:

34555

AN:

53376

Middle Eastern (MID)

AF:

0.543

AC:

3043

AN:

5606

European-Non Finnish (NFE)

AF:

0.588

AC:

610880

AN:

1038942

Other (OTH)

AF:

0.590

AC:

34001

AN:

57650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17038

34076

51114

68152

85190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16420

32840

49260

65680

82100

<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:

0.647

AC:

98376

AN:

152142

Hom.:

32418

Cov.:

AF XY:

0.648

AC XY:

48193

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.775

AC:

32167

AN:

41526

American (AMR)

AF:

0.649

AC:

9923

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2048

AN:

3466

East Asian (EAS)

AF:

0.512

AC:

2640

AN:

5160

South Asian (SAS)

AF:

0.542

AC:

2614

AN:

4824

European-Finnish (FIN)

AF:

0.655

AC:

6932

AN:

10586

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.587

AC:

39926

AN:

67978

Other (OTH)

AF:

0.638

AC:

1348

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1812

3624

5437

7249

9061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.617

Hom.:

6153

Bravo

AF:

0.652

Asia WGS

AF:

0.578

AC:

2013

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

-0.79

CADD

Benign

2.6

(source)

DANN

Benign

0.77

PhyloP100

-0.085

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