rs3210714

chr5-151662371-C-T

Variant summary

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

The NM_003118.4(SPARC):c.*1200G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,502 control chromosomes in the GnomAD database, including 16,163 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 (16096 hom., cov: 33)
  • Exomes 𝑓: 0.55 (67 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.*1200G>A		3_prime_UTR_variant	10/10	ENST00000231061.9
SPARC	NM_001309443.2	c.*1200G>A		3_prime_UTR_variant	10/10
SPARC	NM_001309444.2	c.*1084G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.*1200G>A		3_prime_UTR_variant	10/10	1	NM_003118.4	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67950 AN: 151948 Hom.: 16083 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.546 AC: 238 AN: 436 Hom.: 67 Cov.: 0 AF XY: 0.535 AC XY: 139 AN XY: 260

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.447 AC: 67981 AN: 152066 Hom.: 16096 Cov.: 33 AF XY: 0.450 AC XY: 33439 AN XY: 74318

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.474

Alfa AF: 0.491 Hom.: 24316

Bravo AF: 0.440

Asia WGS AF: 0.431 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.7
Dann	Benign	0.31

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: rs3210714; hg19: chr5-151041932;