chr5-151663542-G-C

Variant names:

• chr5-151663542-G-C
• rs1053411
• NM_003118.4:c.*29C>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.*29C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,605,196 control chromosomes in the GnomAD database, including 25,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2608 hom., cov: 33)
  • Exomes 𝑓: 0.16 (22781 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.373
• Publications: 20 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=-0.75).
• BP6: Variant 5-151663542-G-C is Benign according to our data. Variant chr5-151663542-G-C is described in ClinVar as [Benign]. Clinvar id is 1272922.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.*29C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.939C>G	p.Leu313Leu	synonymous_variant	Exon 10 of 10		NP_001296373.1
SPARC	NM_001309443.2	c.*29C>G		3_prime_UTR_variant	Exon 10 of 10		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.*29C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_003118.4	ENSP00000231061.4
SPARC	ENST00000520687.1	n.544C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26175 AN: 152092 Hom.: 2606 Cov.: 33

Gnomad AFR AF: 0.150

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: 0.148

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.211 AC: 52435 AN: 248960 AF XY: 0.202

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.161 AC: 233765 AN: 1452986 Hom.: 22781 Cov.: 29 AF XY: 0.162 AC XY: 116912 AN XY: 723362

African (AFR) AF: 0.149 AC: 4949 AN: 33284

American (AMR) AF: 0.409 AC: 18239 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4319 AN: 26060

East Asian (EAS) AF: 0.412 AC: 16316 AN: 39638

South Asian (SAS) AF: 0.218 AC: 18706 AN: 85942

European-Finnish (FIN) AF: 0.152 AC: 8087 AN: 53376

Middle Eastern (MID) AF: 0.150 AC: 863 AN: 5750

European-Non Finnish (NFE) AF: 0.138 AC: 152205 AN: 1104250

Other (OTH) AF: 0.168 AC: 10081 AN: 60050

GnomAD4 genome AF: 0.172 AC: 26194 AN: 152210 Hom.: 2608 Cov.: 33 AF XY: 0.177 AC XY: 13174 AN XY: 74408

African (AFR) AF: 0.149 AC: 6206 AN: 41538

American (AMR) AF: 0.300 AC: 4580 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1974 AN: 5178

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4816

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10584

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

European-Non Finnish (NFE) AF: 0.142 AC: 9663 AN: 68018

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.161 Hom.: 392

Bravo AF: 0.181

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	-0.75
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1053411; hg19: chr5-151043103; COSMIC: COSV50557923; COSMIC: COSV50557923;