rs1059279

Positions:

• chr5-151662618-A-C
• chr5-151662618-A-T

Variant summary

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

The NM_003118.4(SPARC):​c.*953T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,688 control chromosomes in the GnomAD database, including 2,120 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 0.14 (2115 hom., cov: 33)
  • Exomes 𝑓: 0.14 (5 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.*953T>G		3_prime_UTR_variant	10/10	ENST00000231061.9
SPARC	NM_001309443.2	c.*953T>G		3_prime_UTR_variant	10/10
SPARC	NM_001309444.2	c.*837T>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.*953T>G		3_prime_UTR_variant	10/10	1	NM_003118.4	P1
SPARC	ENST00000520687.1	n.1468T>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21561 AN: 152138 Hom.: 2112 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.141 AC: 61 AN: 432 Hom.: 5 Cov.: 0 AF XY: 0.163 AC XY: 42 AN XY: 258

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.142 AC: 21579 AN: 152256 Hom.: 2115 Cov.: 33 AF XY: 0.148 AC XY: 10988 AN XY: 74450

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.155

Alfa AF: 0.144 Hom.: 265

Bravo AF: 0.147

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1059279; hg19: chr5-151042179; COSMIC: COSV50559186; COSMIC: COSV50559186;