rs729853

Variant names:

• chr5-151667367-C-T
• rs729853
• NM_003118.4:c.585+100G>A

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.585+100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,397,492 control chromosomes in the GnomAD database, including 23,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2625 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20520 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.937
• 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=-0.82).
• BP6: Variant 5-151667367-C-T is Benign according to our data. Variant chr5-151667367-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.585+100G>A		intron_variant	Intron 7 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.585+100G>A		intron_variant	Intron 7 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.582+100G>A		intron_variant	Intron 7 of 9		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.585+100G>A		intron_variant	Intron 7 of 9	1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26236 AN: 152036 Hom.: 2623 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.164 AC: 204343 AN: 1245336 Hom.: 20520 AF XY: 0.164 AC XY: 103134 AN XY: 627058

African (AFR) AF: 0.149 AC: 4370 AN: 29236

American (AMR) AF: 0.410 AC: 17709 AN: 43236

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 3874 AN: 23342

East Asian (EAS) AF: 0.410 AC: 15732 AN: 38324

South Asian (SAS) AF: 0.218 AC: 16997 AN: 77938

European-Finnish (FIN) AF: 0.152 AC: 7915 AN: 51984

Middle Eastern (MID) AF: 0.150 AC: 796 AN: 5296

European-Non Finnish (NFE) AF: 0.139 AC: 127967 AN: 922964

Other (OTH) AF: 0.169 AC: 8983 AN: 53016

GnomAD4 genome AF: 0.173 AC: 26255 AN: 152156 Hom.: 2625 Cov.: 32 AF XY: 0.177 AC XY: 13201 AN XY: 74380

African (AFR) AF: 0.149 AC: 6198 AN: 41506

American (AMR) AF: 0.300 AC: 4583 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3472

East Asian (EAS) AF: 0.380 AC: 1963 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1071 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1575 AN: 10592

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

European-Non Finnish (NFE) AF: 0.143 AC: 9737 AN: 67994

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.159 Hom.: 8620

Bravo AF: 0.182

Asia WGS AF: 0.302 AC: 1047 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.94
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: rs729853; hg19: chr5-151046928; COSMIC: COSV50561592; COSMIC: COSV50561592;