rs1059279

Variant names:

• chr5-151662618-A-C
• rs1059279
• NM_003118.4:c.*953T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	NM_003118.4	MANE Select	c.*953T>G		3_prime_UTR	Exon 10 of 10	NP_003109.1
	SPARC	NM_001309444.2		c.*837T>G		3_prime_UTR	Exon 10 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.*953T>G		3_prime_UTR	Exon 10 of 10	NP_001296372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.*953T>G		3_prime_UTR	Exon 10 of 10	ENSP00000231061.4
	SPARC	ENST00000896427.1		c.*953T>G		3_prime_UTR	Exon 11 of 11	ENSP00000566486.1
	SPARC	ENST00000896428.1		c.*953T>G		3_prime_UTR	Exon 10 of 10	ENSP00000566487.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.142 AC: 60 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0481 AC: 1998 AN: 41552

American (AMR) AF: 0.285 AC: 4365 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1972 AN: 5182

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10600

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9640 AN: 68010

Other (OTH) AF: 0.155 AC: 328 AN: 2116

Alfa AF: 0.137 Hom.: 816

Bravo AF: 0.147

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.68
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1059279; hg19: chr5-151042179; COSMIC: COSV50559186; COSMIC: COSV50559186;