5-151676076-C-T

Variant names:

• chr5-151676076-C-T
• rs7714314
• NM_003118.4:c.57+56G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003118.4(SPARC):​c.57+56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,299,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.57+56G>A		intron_variant	Intron 2 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.57+56G>A		intron_variant	Intron 2 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.57+56G>A		intron_variant	Intron 2 of 9		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.57+56G>A		intron_variant	Intron 2 of 9	1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1299912 Hom.: 0 AF XY: 0.00000154 AC XY: 1 AN XY: 650584

African (AFR) AF: 0.00 AC: 0 AN: 30362

American (AMR) AF: 0.00 AC: 0 AN: 38754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24560

East Asian (EAS) AF: 0.00 AC: 0 AN: 37940

South Asian (SAS) AF: 0.00 AC: 0 AN: 79002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 977864

Other (OTH) AF: 0.00 AC: 0 AN: 54804

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		-0.047

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: rs7714314; hg19: chr5-151055637;