rs725937

Variant names:

• chr5-151677150-T-C
• rs725937
• NM_003118.4:c.-13-949A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003118.4(SPARC):​c.-13-949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,096 control chromosomes in the GnomAD database, including 29,101 homozygotes. 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: 𝑓 0.61 (29101 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 9 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]

CLMAT3 (HGNC:52287): (colorectal liver metastasis associated transcript 3)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	NM_003118.4	MANE Select	c.-13-949A>G		intron	N/A	NP_003109.1
	SPARC	NM_001309444.2		c.-13-949A>G		intron	N/A	NP_001296373.1
	SPARC	NM_001309443.2		c.-13-949A>G		intron	N/A	NP_001296372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.-13-949A>G		intron	N/A	ENSP00000231061.4
	CLMAT3	ENST00000510576.6	TSL:1	n.103+103T>C		intron	N/A
	SPARC	ENST00000538026.5	TSL:5	c.-65-5456A>G		intron	N/A	ENSP00000440127.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93391 AN: 151976 Hom.: 29073 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.615 AC: 93471 AN: 152094 Hom.: 29101 Cov.: 33 AF XY: 0.616 AC XY: 45832 AN XY: 74368

African (AFR) AF: 0.694 AC: 28790 AN: 41494

American (AMR) AF: 0.630 AC: 9632 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2350 AN: 5176

South Asian (SAS) AF: 0.488 AC: 2352 AN: 4820

European-Finnish (FIN) AF: 0.640 AC: 6757 AN: 10566

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39581 AN: 67966

Other (OTH) AF: 0.609 AC: 1287 AN: 2112

Alfa AF: 0.590 Hom.: 34416

Bravo AF: 0.618

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		0.57
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: rs725937; hg19: chr5-151056711; COSMIC: COSV50557966;