Variant rs2304051 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SPARC	NM_003118.4 linkuse as main transcript	c.120+42T>C	intron_variant	ENST00000231061.9	NP_003109.1
SPARC	NM_001309443.2 linkuse as main transcript	c.117+42T>C	intron_variant		NP_001296372.1
SPARC	NM_001309444.2 linkuse as main transcript	c.120+42T>C	intron_variant		NP_001296373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 linkuse as main transcript	c.120+42T>C		intron_variant		1	NM_003118.4	ENSP00000231061	P1

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

GnomAD3 exomes

AF:

0.101

AC:

25236

AN:

249652

Hom.:

2334

AF XY:

0.0981

AC XY:

13237

AN XY:

134964

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.0564

Gnomad4 ASJ exome

AF:

0.0790

Gnomad4 EAS exome

AF:

0.0743

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0798

Gnomad4 NFE exome

AF:

0.0723

Gnomad4 OTH exome

AF:

0.0987

GnomAD4 genome

AF:

0.173

AC:

26238

AN:

152082

Hom.:

4098

Cov.:

AF XY:

0.171

AC XY:

12703

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.0887

Gnomad4 ASJ

AF:

0.0893

Gnomad4 EAS

AF:

0.0650

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.0877

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.0525

Hom.:

Bravo

AF:

0.183

Asia WGS

AF:

0.114

AC:

400

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.25

DANN

Benign

0.41

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