dbSNP rs1054204: SPARC:c.*582G>C (chr5-151662989-C-G) – 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.*582G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,260 control chromosomes in the GnomAD database, including 16,171 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 0.45 ( 16153 hom., cov: 33)

Exomes 𝑓: 0.57 ( 18 hom. )

Consequence

SPARC
NM_003118.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.101

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, 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4 link	c.*582G>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000231061.9	NP_003109.1	P09486
SPARC	NM_001309444.2 link	c.*466G>C	3_prime_UTR_variant	Exon 10 of 10		NP_001296373.1	P09486
SPARC	NM_001309443.2 link	c.*582G>C	3_prime_UTR_variant	Exon 10 of 10		NP_001296372.1	P09486

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 link	c.*582G>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_003118.4	ENSP00000231061.4		P09486
SPARC	ENST00000520687.1 link	n.1097G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68089

AN:

152034

Hom.:

16140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.469

GnomAD4 exome

AF:

0.574

AC:

AN:

108

Hom.:

Cov.:

AF XY:

0.597

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.667

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.563

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.448

AC:

68120

AN:

152152

Hom.:

16153

Cov.:

AF XY:

0.451

AC XY:

33534

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.283

AC:

11735

AN:

41512

American (AMR)

AF:

0.546

AC:

8346

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1718

AN:

3466

East Asian (EAS)

AF:

0.431

AC:

2229

AN:

5166

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4826

European-Finnish (FIN)

AF:

0.554

AC:

5870

AN:

10598

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.511

AC:

34714

AN:

67986

Other (OTH)

AF:

0.472

AC:

994

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1892

3784

5676

7568

9460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.473

Hom.:

2188

Bravo

AF:

0.441

Asia WGS

AF:

0.430

AC:

1495

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Osteogenesis imperfecta

Benign:1

May 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.81

CADD

Benign

4.2

(source)

DANN

Benign

0.69

PhyloP100

-0.10

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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rs1054204

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