rs1059829

Positions:

• chr5-151662468-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003118.4(SPARC):​c.*1103C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,454 control chromosomes in the GnomAD database, including 16,283 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16216 hom., cov: 32)
  • Exomes 𝑓: 0.55 (67 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPARC	NM_003118.4	c.*1103C>T		3_prime_UTR_variant	10/10	ENST00000231061.9	NP_003109.1
SPARC	NM_001309443.2	c.*1103C>T		3_prime_UTR_variant	10/10		NP_001296372.1
SPARC	NM_001309444.2	c.*987C>T		3_prime_UTR_variant	10/10		NP_001296373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.*1103C>T		3_prime_UTR_variant	10/10	1	NM_003118.4	ENSP00000231061	P1
SPARC	ENST00000520687.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68342 AN: 151904 Hom.: 16203 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.548 AC: 238 AN: 434 Hom.: 67 Cov.: 0 AF XY: 0.534 AC XY: 140 AN XY: 262

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.450 AC: 68375 AN: 152020 Hom.: 16216 Cov.: 32 AF XY: 0.453 AC XY: 33630 AN XY: 74300

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.474

Alfa AF: 0.492 Hom.: 19709

Bravo AF: 0.443

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.81

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: rs1059829; hg19: chr5-151042029; COSMIC: COSV50558540; COSMIC: COSV50558540;