rs1054204

Positions:

• chr5-151662989-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.*582G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,260 control chromosomes in the GnomAD database, including 16,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16153 hom., cov: 33)
  • Exomes 𝑓: 0.57 (18 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.101

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]

SPARC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-151662989-C-G is Benign according to our data. Variant chr5-151662989-C-G is described in ClinVar as [Benign]. Clinvar id is 1702066.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	Protein	UniProt
SPARC	NM_003118.4	c.*582G>C		3_prime_UTR_variant	10/10	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.*466G>C		3_prime_UTR_variant	10/10		NP_001296373.1
SPARC	NM_001309443.2	c.*582G>C		3_prime_UTR_variant	10/10		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.*582G>C		3_prime_UTR_variant	10/10	1	NM_003118.4	ENSP00000231061.4
SPARC	ENST00000520687.1	n.1097G>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68089 AN: 152034 Hom.: 16140 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.574 AC: 62 AN: 108 Hom.: 18 Cov.: 0 AF XY: 0.597 AC XY: 37 AN XY: 62

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.448 AC: 68120 AN: 152152 Hom.: 16153 Cov.: 33 AF XY: 0.451 AC XY: 33534 AN XY: 74404

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.472

Alfa AF: 0.473 Hom.: 2188

Bravo AF: 0.441

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Osteogenesis imperfecta Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 21, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.69

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: rs1054204; hg19: chr5-151042550;