5-151663652-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.884-53C>T		intron_variant		ENST00000231061.9
SPARC	NM_001309443.2	c.881-53C>T		intron_variant
SPARC	NM_001309444.2	c.884-55C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.884-53C>T		intron_variant		1	NM_003118.4	P1
SPARC	ENST00000520687.1	n.487-53C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.169

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

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.186

Alfa AF: 0.159 Hom.: 371

Bravo AF: 0.181

Asia WGS AF: 0.302 AC: 1048 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.030
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs11950384; hg19: chr5-151043213; COSMIC: COSV50557926; COSMIC: COSV50557926;