Variant rs2304052 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003118.4(SPARC):c.66A>G(p.Glu22=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE
SPARC	NM_003118.4 linkuse as main transcript	c.66A>G	p.Glu22=	synonymous_variant	3/10	ENST00000231061.9
SPARC	NM_001309444.2 linkuse as main transcript	c.66A>G	p.Glu22=	synonymous_variant	3/10
SPARC	NM_001309443.2 linkuse as main transcript	c.63A>G	p.Glu21=	synonymous_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9 linkuse as main transcript	c.66A>G	p.Glu22=	synonymous_variant	3/10	1	NM_003118.4	P1

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

GnomAD3 exomes

AF:

0.101

AC:

25390

AN:

251106

Hom.:

2345

AF XY:

0.0982

AC XY:

13327

AN XY:

135696

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.0565

Gnomad4 ASJ exome

AF:

0.0791

Gnomad4 EAS exome

AF:

0.0742

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0800

Gnomad4 NFE exome

AF:

0.0727

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.173

AC:

26281

AN:

152154

Hom.:

4106

Cov.:

AF XY:

0.171

AC XY:

12719

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.0887

Gnomad4 ASJ

AF:

0.0896

Gnomad4 EAS

AF:

0.0645

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.0881

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.0891

Hom.:

1953

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Osteogenesis imperfecta type 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over