rs2116780

Variant names:

• chr5-151674576-A-C
• rs2116780
• NM_003118.4:c.120+36T>G

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.120+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,604,502 control chromosomes in the GnomAD database, including 25,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2677 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22989 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.716
• Publications: 12 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, Ambry Genetics, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae)
• 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=-0.85).
• BP6: Variant 5-151674576-A-C is Benign according to our data. Variant chr5-151674576-A-C is described in ClinVar as Benign. ClinVar VariationId is 1242259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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.120+36T>G		intron	N/A	NP_003109.1	P09486
	SPARC	NM_001309444.2		c.120+36T>G		intron	N/A	NP_001296373.1
	SPARC	NM_001309443.2		c.117+36T>G		intron	N/A	NP_001296372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.120+36T>G		intron	N/A	ENSP00000231061.4	P09486
	SPARC	ENST00000896427.1		c.120+36T>G		intron	N/A	ENSP00000566486.1
	SPARC	ENST00000896428.1		c.120+36T>G		intron	N/A	ENSP00000566487.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26468 AN: 151990 Hom.: 2674 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.211 AC: 52771 AN: 250540 AF XY: 0.202

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.369

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.162 AC: 236000 AN: 1452394 Hom.: 22989 Cov.: 29 AF XY: 0.163 AC XY: 118008 AN XY: 723268

African (AFR) AF: 0.159 AC: 5273 AN: 33234

American (AMR) AF: 0.409 AC: 18214 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4333 AN: 26040

East Asian (EAS) AF: 0.409 AC: 16211 AN: 39652

South Asian (SAS) AF: 0.220 AC: 18941 AN: 86018

European-Finnish (FIN) AF: 0.151 AC: 8087 AN: 53392

Middle Eastern (MID) AF: 0.154 AC: 887 AN: 5750

European-Non Finnish (NFE) AF: 0.139 AC: 153942 AN: 1103682

Other (OTH) AF: 0.168 AC: 10112 AN: 60066

GnomAD4 genome AF: 0.174 AC: 26489 AN: 152108 Hom.: 2677 Cov.: 32 AF XY: 0.179 AC XY: 13310 AN XY: 74346

African (AFR) AF: 0.157 AC: 6492 AN: 41464

American (AMR) AF: 0.300 AC: 4587 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5162

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1563 AN: 10578

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9691 AN: 68012

Other (OTH) AF: 0.184 AC: 390 AN: 2114

Alfa AF: 0.159 Hom.: 452

Bravo AF: 0.184

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.55
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2116780; hg19: chr5-151054137; COSMIC: COSV107220545; COSMIC: COSV107220545;