rs7719521

Variant names:

• chr5-151669843-A-C
• rs7719521
• NM_003118.4:c.331-59T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-151669843-A-C
• chr5-151669843-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003118.4(SPARC):​c.331-59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,600,710 control chromosomes in the GnomAD database, including 289,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (32461 hom., cov: 32)
  • Exomes 𝑓: 0.59 (257042 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-151669843-A-C is Benign according to our data. Variant chr5-151669843-A-C is described in ClinVar as [Benign]. Clinvar id is 1263260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.331-59T>G		intron_variant	Intron 5 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.331-59T>G		intron_variant	Intron 5 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.328-59T>G		intron_variant	Intron 5 of 9		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.331-59T>G		intron_variant	Intron 5 of 9	1	NM_003118.4	ENSP00000231061.4
SPARC	ENST00000538026.5	c.58-59T>G		intron_variant	Intron 2 of 4	5		ENSP00000440127.1
SPARC	ENST00000521569.1	c.58-59T>G		intron_variant	Intron 3 of 5	2		ENSP00000428119.1
SPARC	ENST00000524277.1	n.258-59T>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98340 AN: 151910 Hom.: 32414 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.594 AC: 859803 AN: 1448682 Hom.: 257042 AF XY: 0.590 AC XY: 424859 AN XY: 719664

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.648 AC: 98443 AN: 152028 Hom.: 32461 Cov.: 32 AF XY: 0.649 AC XY: 48235 AN XY: 74298

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.641

Alfa AF: 0.590 Hom.: 54661

Bravo AF: 0.653

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.66

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: rs7719521; hg19: chr5-151049404; COSMIC: COSV50558542; COSMIC: COSV50558542;