dbSNP rs7719521: SPARC:c.331-59T>G (chr5-151669843-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003118.4(SPARC):c.331-59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,600,710 control chromosomes in the GnomAD database, including 289,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 32461 hom., cov: 32)

Exomes 𝑓: 0.59 ( 257042 hom. )

Consequence

SPARC
NM_003118.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0290

Publications

22 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-151669843-A-C is Benign according to our data. Variant chr5-151669843-A-C is described in ClinVar as Benign. ClinVar VariationId is 1263260.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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.331-59T>G	intron	N/A	NP_003109.1	P09486
SPARC	NM_001309444.2		c.331-59T>G	intron	N/A	NP_001296373.1
SPARC	NM_001309443.2		c.328-59T>G	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.331-59T>G	intron	N/A	ENSP00000231061.4	P09486
SPARC	ENST00000896427.1		c.331-59T>G	intron	N/A	ENSP00000566486.1
SPARC	ENST00000896428.1		c.331-59T>G	intron	N/A	ENSP00000566487.1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98340

AN:

151910

Hom.:

32414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.636

GnomAD4 exome

AF:

0.594

AC:

859803

AN:

1448682

Hom.:

257042

AF XY:

0.590

AC XY:

424859

AN XY:

719664

show subpopulations

African (AFR)

AF:

0.790

AC:

26345

AN:

33344

American (AMR)

AF:

0.658

AC:

29100

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

14813

AN:

25240

East Asian (EAS)

AF:

0.536

AC:

21193

AN:

39558

South Asian (SAS)

AF:

0.542

AC:

45790

AN:

84478

European-Finnish (FIN)

AF:

0.647

AC:

34263

AN:

52916

Middle Eastern (MID)

AF:

0.543

AC:

3103

AN:

5716

European-Non Finnish (NFE)

AF:

0.589

AC:

649833

AN:

1103372

Other (OTH)

AF:

0.591

AC:

35363

AN:

59828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

17355

34710

52065

69420

86775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18018

36036

54054

72072

90090

<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:

0.648

AC:

98443

AN:

152028

Hom.:

32461

Cov.:

AF XY:

0.649

AC XY:

48235

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.776

AC:

32204

AN:

41498

American (AMR)

AF:

0.650

AC:

9924

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2051

AN:

3472

East Asian (EAS)

AF:

0.515

AC:

2652

AN:

5152

South Asian (SAS)

AF:

0.542

AC:

2612

AN:

4818

European-Finnish (FIN)

AF:

0.655

AC:

6917

AN:

10562

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39950

AN:

67936

Other (OTH)

AF:

0.641

AC:

1352

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1779

3558

5337

7116

8895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.603

Hom.:

119930

Bravo

AF:

0.653

Asia WGS

AF:

0.582

AC:

2025

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

(source)

DANN

Benign

0.66

PhyloP100

-0.029

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