rs1054204

Variant names:

• chr5-151662989-C-G
• rs1054204
• NM_003118.4:c.*582G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 17

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	NM_003118.4	MANE Select	c.*582G>C		3_prime_UTR	Exon 10 of 10	NP_003109.1
	SPARC	NM_001309444.2		c.*466G>C		3_prime_UTR	Exon 10 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.*582G>C		3_prime_UTR	Exon 10 of 10	NP_001296372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.*582G>C		3_prime_UTR	Exon 10 of 10	ENSP00000231061.4
	SPARC	ENST00000520687.1	TSL:2	n.1097G>C		non_coding_transcript_exon	Exon 4 of 4

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.667 AC: 4 AN: 6

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 54 AN: 96

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.283 AC: 11735 AN: 41512

American (AMR) AF: 0.546 AC: 8346 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1718 AN: 3466

East Asian (EAS) AF: 0.431 AC: 2229 AN: 5166

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4826

European-Finnish (FIN) AF: 0.554 AC: 5870 AN: 10598

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34714 AN: 67986

Other (OTH) AF: 0.472 AC: 994 AN: 2104

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

May 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1054204; hg19: chr5-151042550;