rs1060151

Variant names:

• chr5-151663423-A-T
• rs1060151
• NM_003118.4:c.*148T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151663423-A-T
• chr5-151663423-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003118.4(SPARC):​c.*148T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 768,866 control chromosomes in the GnomAD database, including 600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (103 hom., cov: 33)
  • Exomes 𝑓: 0.036 (497 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.985
• 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, Ambry Genetics, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-151663423-A-T is Benign according to our data. Variant chr5-151663423-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1317768.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 = 0.0282 (4293/152286) while in subpopulation NFE AF = 0.0438 (2982/68024). AF 95% confidence interval is 0.0425. There are 103 homozygotes in GnomAd4. There are 2047 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 103 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	NM_003118.4	MANE Select	c.*148T>A		3_prime_UTR	Exon 10 of 10	NP_003109.1	P09486
	SPARC	NM_001309444.2		c.*32T>A		3_prime_UTR	Exon 10 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.*148T>A		3_prime_UTR	Exon 10 of 10	NP_001296372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.*148T>A		3_prime_UTR	Exon 10 of 10	ENSP00000231061.4	P09486
	SPARC	ENST00000896427.1		c.*148T>A		3_prime_UTR	Exon 11 of 11	ENSP00000566486.1
	SPARC	ENST00000896428.1		c.*148T>A		3_prime_UTR	Exon 10 of 10	ENSP00000566487.1

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4294 AN: 152170 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.0361 AC: 22237 AN: 616580 Hom.: 497 Cov.: 8 AF XY: 0.0354 AC XY: 11485 AN XY: 324210

African (AFR) AF: 0.00728 AC: 115 AN: 15798

American (AMR) AF: 0.0140 AC: 370 AN: 26400

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 275 AN: 15496

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34324

South Asian (SAS) AF: 0.0158 AC: 844 AN: 53352

European-Finnish (FIN) AF: 0.0445 AC: 2002 AN: 45004

Middle Eastern (MID) AF: 0.0183 AC: 67 AN: 3654

European-Non Finnish (NFE) AF: 0.0448 AC: 17527 AN: 390934

Other (OTH) AF: 0.0328 AC: 1036 AN: 31618

GnomAD4 genome AF: 0.0282 AC: 4293 AN: 152286 Hom.: 103 Cov.: 33 AF XY: 0.0275 AC XY: 2047 AN XY: 74452

African (AFR) AF: 0.00871 AC: 362 AN: 41558

American (AMR) AF: 0.0170 AC: 260 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4822

European-Finnish (FIN) AF: 0.0448 AC: 475 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2982 AN: 68024

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0331 Hom.: 12

Bravo AF: 0.0254

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.0
DANN	Benign	0.87
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism

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: rs1060151; hg19: chr5-151042984;