5-151663981-C-G

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.883+106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,354,566 control chromosomes in the GnomAD database, including 1,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (140 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1505 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276

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=-0.7).
• BP6: Variant 5-151663981-C-G is Benign according to our data. Variant chr5-151663981-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.883+106G>C		intron_variant		ENST00000231061.9
SPARC	NM_001309443.2	c.880+106G>C		intron_variant
SPARC	NM_001309444.2	c.883+106G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.883+106G>C		intron_variant		1	NM_003118.4	P1
SPARC	ENST00000520687.1	n.486+106G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5214 AN: 152194 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0415

GnomAD4 exome AF: 0.0466 AC: 56004 AN: 1202254 Hom.: 1505 AF XY: 0.0458 AC XY: 27667 AN XY: 604564

Gnomad4 AFR exome AF: 0.00785

Gnomad4 AMR exome AF: 0.0215

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.0000522

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0461

Gnomad4 NFE exome AF: 0.0547

Gnomad4 OTH exome AF: 0.0403

GnomAD4 genome AF: 0.0343 AC: 5225 AN: 152312 Hom.: 140 Cov.: 32 AF XY: 0.0334 AC XY: 2489 AN XY: 74464

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0397 Hom.: 15

Bravo AF: 0.0317

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	5.4
Dann	Benign	0.78

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: rs41290585; hg19: chr5-151043542; COSMIC: COSV50560736; COSMIC: COSV50560736;