chr5-151678618-G-A

Position:

• chr5-151678618-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003118.4(SPARC):​c.-13-2417C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 152,226 control chromosomes in the GnomAD database, including 319 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 0.061 (319 hom., cov: 32)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPARC	NM_003118.4	c.-13-2417C>T		intron_variant		ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.-13-2417C>T		intron_variant			NP_001296373.1
SPARC	NM_001309443.2	c.-13-2417C>T		intron_variant			NP_001296372.1
CLMAT3	NR_109873.1	n.104-602G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.-13-2417C>T		intron_variant		1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9223 AN: 152108 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0607 AC: 9239 AN: 152226 Hom.: 319 Cov.: 32 AF XY: 0.0633 AC XY: 4713 AN XY: 74426

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.0580

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0862

Gnomad4 NFE AF: 0.0682

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0693 Hom.: 230

Bravo AF: 0.0557

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.61

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: rs17718324; hg19: chr5-151058179;