rs729853

Positions:

• chr5-151667367-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003118.4(SPARC):​c.585+100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,397,492 control chromosomes in the GnomAD database, including 23,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2625 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20520 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.937

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-151667367-C-T is Benign according to our data. Variant chr5-151667367-C-T is described in ClinVar as [Benign]. Clinvar id is 1237216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.585+100G>A		intron_variant		ENST00000231061.9
SPARC	NM_001309443.2	c.582+100G>A		intron_variant
SPARC	NM_001309444.2	c.585+100G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.585+100G>A		intron_variant		1	NM_003118.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26236 AN: 152036 Hom.: 2623 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.164 AC: 204343 AN: 1245336 Hom.: 20520 AF XY: 0.164 AC XY: 103134 AN XY: 627058

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.173 AC: 26255 AN: 152156 Hom.: 2625 Cov.: 32 AF XY: 0.177 AC XY: 13201 AN XY: 74380

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.184

Alfa AF: 0.154 Hom.: 3562

Bravo AF: 0.182

Asia WGS AF: 0.302 AC: 1047 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs729853; hg19: chr5-151046928; COSMIC: COSV50561592; COSMIC: COSV50561592;