5-151663455-CTA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003118.4(SPARC):c.*114_*115del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0208 in 993,070 control chromosomes in the GnomAD database, including 254 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (22 hom., cov: 32)
  • Exomes 𝑓: 0.022 (232 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.54

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 -16 ACMG points.

• BP6: Variant 5-151663455-CTA-C is Benign according to our data. Variant chr5-151663455-CTA-C is described in ClinVar as [Likely_benign]. Clinvar id is 2920766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2254/152312) while in subpopulation NFE AF= 0.0235 (1602/68030). AF 95% confidence interval is 0.0226. There are 22 homozygotes in gnomad4. There are 1057 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.*114_*115del		3_prime_UTR_variant	10/10	ENST00000231061.9
SPARC	NM_001309444.2	c.1024_1025del	p.Ter342AspfsTer64	frameshift_variant, stop_lost	10/10
SPARC	NM_001309443.2	c.*114_*115del		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.*114_*115del		3_prime_UTR_variant	10/10	1	NM_003118.4	P1
SPARC	ENST00000520687.1	n.629_630del		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2252 AN: 152194 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00451

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0219 AC: 18398 AN: 840758 Hom.: 232 AF XY: 0.0220 AC XY: 9634 AN XY: 437508

Gnomad4 AFR exome AF: 0.00436

Gnomad4 AMR exome AF: 0.00766

Gnomad4 ASJ exome AF: 0.00530

Gnomad4 EAS exome AF: 0.000387

Gnomad4 SAS exome AF: 0.0186

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0266

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0148 AC: 2254 AN: 152312 Hom.: 22 Cov.: 32 AF XY: 0.0142 AC XY: 1057 AN XY: 74476

Gnomad4 AFR AF: 0.00450

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0173 Hom.: 1

Bravo AF: 0.0137

Asia WGS AF: 0.00866 AC: 31 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis imperfecta type 17 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 16, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

SPARC: PM4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs71757813; hg19: chr5-151043016;