rs11950384

Variant names:

• chr5-151663652-G-A
• rs11950384
• NM_003118.4:c.884-53C>T

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.884-53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,592,466 control chromosomes in the GnomAD database, including 25,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2603 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22765 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13
• Publications: 9 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=-0.94).
• BP6: Variant 5-151663652-G-A is Benign according to our data. Variant chr5-151663652-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291605.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	NM_003118.4	MANE Select	c.884-53C>T		intron	N/A	NP_003109.1
	SPARC	NM_001309444.2		c.884-55C>T		intron	N/A	NP_001296373.1
	SPARC	NM_001309443.2		c.881-53C>T		intron	N/A	NP_001296372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.884-53C>T		intron	N/A	ENSP00000231061.4
	SPARC	ENST00000520687.1	TSL:2	n.487-53C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26136 AN: 151976 Hom.: 2601 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.162 AC: 233251 AN: 1440372 Hom.: 22765 AF XY: 0.162 AC XY: 116650 AN XY: 717870

African (AFR) AF: 0.150 AC: 4955 AN: 33066

American (AMR) AF: 0.408 AC: 18232 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4310 AN: 25986

East Asian (EAS) AF: 0.411 AC: 16282 AN: 39576

South Asian (SAS) AF: 0.218 AC: 18680 AN: 85716

European-Finnish (FIN) AF: 0.151 AC: 7995 AN: 52792

Middle Eastern (MID) AF: 0.151 AC: 862 AN: 5720

European-Non Finnish (NFE) AF: 0.139 AC: 151851 AN: 1093188

Other (OTH) AF: 0.169 AC: 10084 AN: 59696

GnomAD4 genome AF: 0.172 AC: 26155 AN: 152094 Hom.: 2603 Cov.: 32 AF XY: 0.177 AC XY: 13153 AN XY: 74354

African (AFR) AF: 0.149 AC: 6178 AN: 41460

American (AMR) AF: 0.300 AC: 4583 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 557 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1964 AN: 5154

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1573 AN: 10592

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9649 AN: 67998

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.159 Hom.: 381

Bravo AF: 0.181

Asia WGS AF: 0.302 AC: 1048 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.94
CADD	Benign	0.030
DANN	Benign	0.61
PhyloP100		-2.1
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: rs11950384; hg19: chr5-151043213; COSMIC: COSV50557926; COSMIC: COSV50557926;