rs3210714

Variant names:

• chr5-151662371-C-T
• rs3210714
• NM_003118.4:c.*1200G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.82).
• 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.*1200G>A		3_prime_UTR	Exon 10 of 10	NP_003109.1
	SPARC	NM_001309444.2		c.*1084G>A		3_prime_UTR	Exon 10 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.*1200G>A		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.*1200G>A		3_prime_UTR	Exon 10 of 10	ENSP00000231061.4
	SPARC	ENST00000520687.1	TSL:2	n.*117G>A		downstream_gene	N/A

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

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: 0.333 AC: 2 AN: 6

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.281 AC: 11634 AN: 41456

American (AMR) AF: 0.546 AC: 8356 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2224 AN: 5170

South Asian (SAS) AF: 0.371 AC: 1786 AN: 4812

European-Finnish (FIN) AF: 0.554 AC: 5854 AN: 10560

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

European-Non Finnish (NFE) AF: 0.510 AC: 34659 AN: 67984

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

Alfa AF: 0.487 Hom.: 30597

Bravo AF: 0.440

Asia WGS AF: 0.431 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.31
PhyloP100		-0.18
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: rs3210714; hg19: chr5-151041932;