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. The variant received -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
• Publications: 22 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, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

African (AFR) AF: 0.790 AC: 26345 AN: 33344

American (AMR) AF: 0.658 AC: 29100 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 14813 AN: 25240

East Asian (EAS) AF: 0.536 AC: 21193 AN: 39558

South Asian (SAS) AF: 0.542 AC: 45790 AN: 84478

European-Finnish (FIN) AF: 0.647 AC: 34263 AN: 52916

Middle Eastern (MID) AF: 0.543 AC: 3103 AN: 5716

European-Non Finnish (NFE) AF: 0.589 AC: 649833 AN: 1103372

Other (OTH) AF: 0.591 AC: 35363 AN: 59828

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

African (AFR) AF: 0.776 AC: 32204 AN: 41498

American (AMR) AF: 0.650 AC: 9924 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2652 AN: 5152

South Asian (SAS) AF: 0.542 AC: 2612 AN: 4818

European-Finnish (FIN) AF: 0.655 AC: 6917 AN: 10562

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39950 AN: 67936

Other (OTH) AF: 0.641 AC: 1352 AN: 2110

Alfa AF: 0.603 Hom.: 119930

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		-0.029
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: rs7719521; hg19: chr5-151049404; COSMIC: COSV50558542; COSMIC: COSV50558542;