rs2116780

Positions:

• chr5-151674576-A-C

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.120+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,604,502 control chromosomes in the GnomAD database, including 25,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2677 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22989 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.716

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=-0.85).
• BP6: Variant 5-151674576-A-C is Benign according to our data. Variant chr5-151674576-A-C is described in ClinVar as [Benign]. Clinvar id is 1242259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.120+36T>G		intron_variant		ENST00000231061.9
SPARC	NM_001309443.2	c.117+36T>G		intron_variant
SPARC	NM_001309444.2	c.120+36T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.120+36T>G		intron_variant		1	NM_003118.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26468 AN: 151990 Hom.: 2674 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.211 AC: 52771 AN: 250540 Hom.: 7303 AF XY: 0.202 AC XY: 27372 AN XY: 135426

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.162 AC: 236000 AN: 1452394 Hom.: 22989 Cov.: 29 AF XY: 0.163 AC XY: 118008 AN XY: 723268

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.174 AC: 26489 AN: 152108 Hom.: 2677 Cov.: 32 AF XY: 0.179 AC XY: 13310 AN XY: 74346

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.184

Alfa AF: 0.160 Hom.: 442

Bravo AF: 0.184

Asia WGS AF: 0.300 AC: 1041 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	-0.85
CADD	Benign	5.6
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2116780; hg19: chr5-151054137;