5-151662468-G-A

Variant names:

• chr5-151662468-G-A
• rs1059829
• NM_003118.4:c.*1103C>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.*1103C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,454 control chromosomes in the GnomAD database, including 16,283 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 (16216 hom., cov: 32)
  • Exomes 𝑓: 0.55 (67 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 21 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 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.*1103C>T		3_prime_UTR	Exon 10 of 10	NP_003109.1
	SPARC	NM_001309444.2		c.*987C>T		3_prime_UTR	Exon 10 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.*1103C>T		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.*1103C>T		3_prime_UTR	Exon 10 of 10	ENSP00000231061.4
	SPARC	ENST00000520687.1	TSL:2	n.*20C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68342 AN: 151904 Hom.: 16203 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.548 AC: 238 AN: 434 Hom.: 67 Cov.: 0 AF XY: 0.534 AC XY: 140 AN XY: 262

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: 0.547 AC: 233 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.450 AC: 68375 AN: 152020 Hom.: 16216 Cov.: 32 AF XY: 0.453 AC XY: 33630 AN XY: 74300

African (AFR) AF: 0.290 AC: 12029 AN: 41454

American (AMR) AF: 0.547 AC: 8364 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5168

South Asian (SAS) AF: 0.372 AC: 1788 AN: 4812

European-Finnish (FIN) AF: 0.554 AC: 5838 AN: 10544

Middle Eastern (MID) AF: 0.517 AC: 150 AN: 290

European-Non Finnish (NFE) AF: 0.510 AC: 34664 AN: 67982

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.487 Hom.: 55285

Bravo AF: 0.443

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		1.8
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: rs1059829; hg19: chr5-151042029; COSMIC: COSV50558540; COSMIC: COSV50558540;