chr5-151676076-C-G

Variant names:

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

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.57+56G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 1,450,910 control chromosomes in the GnomAD database, including 10,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (3511 hom., cov: 32)
  • Exomes 𝑓: 0.085 (6690 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-151676076-C-G is Benign according to our data. Variant chr5-151676076-C-G is described in ClinVar as [Benign]. Clinvar id is 1281906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.57+56G>C		intron_variant	Intron 2 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.57+56G>C		intron_variant	Intron 2 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.57+56G>C		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>C		intron_variant	Intron 2 of 9	1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24755 AN: 151904 Hom.: 3494 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.0850 AC: 110359 AN: 1298890 Hom.: 6690 AF XY: 0.0860 AC XY: 55924 AN XY: 650082

African (AFR) AF: 0.401 AC: 12141 AN: 30304

American (AMR) AF: 0.0577 AC: 2235 AN: 38738

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 1916 AN: 24546

East Asian (EAS) AF: 0.0750 AC: 2846 AN: 37926

South Asian (SAS) AF: 0.137 AC: 10819 AN: 78960

European-Finnish (FIN) AF: 0.0795 AC: 4067 AN: 51144

Middle Eastern (MID) AF: 0.103 AC: 563 AN: 5456

European-Non Finnish (NFE) AF: 0.0721 AC: 70480 AN: 977058

Other (OTH) AF: 0.0966 AC: 5292 AN: 54758

GnomAD4 genome AF: 0.163 AC: 24810 AN: 152020 Hom.: 3511 Cov.: 32 AF XY: 0.162 AC XY: 12027 AN XY: 74296

African (AFR) AF: 0.386 AC: 15983 AN: 41430

American (AMR) AF: 0.0894 AC: 1366 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 311 AN: 3464

East Asian (EAS) AF: 0.0645 AC: 333 AN: 5160

South Asian (SAS) AF: 0.139 AC: 671 AN: 4826

European-Finnish (FIN) AF: 0.0886 AC: 935 AN: 10554

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4848 AN: 67992

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.0305 Hom.: 28

Bravo AF: 0.173

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 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	-0.85
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		-0.047
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: rs7714314; hg19: chr5-151055637; COSMIC: COSV50561227; COSMIC: COSV50561227;