rs2304051

Variant names:

• chr5-151674570-A-G
• rs2304051
• NM_003118.4:c.120+42T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-151674570-A-G
• chr5-151674570-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003118.4(SPARC):​c.120+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 1,591,912 control chromosomes in the GnomAD database, including 11,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (4098 hom., cov: 32)
  • Exomes 𝑓: 0.086 (7856 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.57

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-151674570-A-G is Benign according to our data. Variant chr5-151674570-A-G is described in ClinVar as [Benign]. Clinvar id is 1296627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.120+42T>C		intron_variant	Intron 3 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.120+42T>C		intron_variant	Intron 3 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.117+42T>C		intron_variant	Intron 3 of 9		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.120+42T>C		intron_variant	Intron 3 of 9	1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26176 AN: 151964 Hom.: 4077 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.101 AC: 25236 AN: 249652 AF XY: 0.0981

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.0525

Gnomad ASJ exome AF: 0.0817

Gnomad EAS exome AF: 0.0660

Gnomad FIN exome AF: 0.0807

Gnomad NFE exome AF: 0.0712

Gnomad OTH exome AF: 0.0777

GnomAD4 exome AF: 0.0857 AC: 123408 AN: 1439830 Hom.: 7856 Cov.: 26 AF XY: 0.0868 AC XY: 62319 AN XY: 717820

Gnomad4 AFR exome AF: 0.438 AC: 14375 AN: 32816

Gnomad4 AMR exome AF: 0.0564 AC: 2506 AN: 44422

Gnomad4 ASJ exome AF: 0.0790 AC: 2047 AN: 25898

Gnomad4 EAS exome AF: 0.0743 AC: 2943 AN: 39600

Gnomad4 SAS exome AF: 0.138 AC: 11781 AN: 85630

Gnomad4 FIN exome AF: 0.0798 AC: 4255 AN: 53338

Gnomad4 NFE exome AF: 0.0723 AC: 79005 AN: 1092728

Gnomad4 Remaining exome AF: 0.0987 AC: 5892 AN: 59680

GnomAD4 genome AF: 0.173 AC: 26238 AN: 152082 Hom.: 4098 Cov.: 32 AF XY: 0.171 AC XY: 12703 AN XY: 74356

Gnomad4 AFR AF: 0.420 AC: 0.420418 AN: 0.420418

Gnomad4 AMR AF: 0.0887 AC: 0.0886854 AN: 0.0886854

Gnomad4 ASJ AF: 0.0893 AC: 0.0893372 AN: 0.0893372

Gnomad4 EAS AF: 0.0650 AC: 0.0650077 AN: 0.0650077

Gnomad4 SAS AF: 0.139 AC: 0.138704 AN: 0.138704

Gnomad4 FIN AF: 0.0877 AC: 0.0877077 AN: 0.0877077

Gnomad4 NFE AF: 0.0713 AC: 0.071313 AN: 0.071313

Gnomad4 OTH AF: 0.153 AC: 0.153409 AN: 0.153409

Alfa AF: 0.0640 Hom.: 146

Bravo AF: 0.183

Asia WGS AF: 0.114 AC: 400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis imperfecta type 17 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.91
CADD	Benign	0.25
DANN	Benign	0.41
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

Publications

LitVar

Other links and lift over

dbSNP: rs2304051; hg19: chr5-151054131; COSMIC: COSV50558580; COSMIC: COSV50558580;