rs1978707

Variant names:

• chr5-151673098-G-A
• rs1978707
• NM_003118.4:c.208+31C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151673098-G-A
• chr5-151673098-G-C
• chr5-151673098-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003118.4(SPARC):​c.208+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,533,806 control chromosomes in the GnomAD database, including 277,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32418 hom., cov: 33)
  • Exomes 𝑓: 0.59 (244776 hom.)
• Consequence: SPARC NM_003118.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0850
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-151673098-G-A is Benign according to our data. Variant chr5-151673098-G-A is described in ClinVar as Benign. ClinVar VariationId is 1278457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4	c.208+31C>T		intron_variant	Intron 4 of 9	ENST00000231061.9	NP_003109.1
SPARC	NM_001309444.2	c.208+31C>T		intron_variant	Intron 4 of 9		NP_001296373.1
SPARC	NM_001309443.2	c.205+31C>T		intron_variant	Intron 4 of 9		NP_001296372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9	c.208+31C>T		intron_variant	Intron 4 of 9	1	NM_003118.4	ENSP00000231061.4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98276 AN: 152022 Hom.: 32374 Cov.: 33

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.605 AC: 151939 AN: 251256 AF XY: 0.596

Gnomad AFR exome AF: 0.783

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.592

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.593 AC: 818919 AN: 1381664 Hom.: 244776 Cov.: 22 AF XY: 0.589 AC XY: 408102 AN XY: 692384

African (AFR) AF: 0.788 AC: 25136 AN: 31886

American (AMR) AF: 0.657 AC: 29347 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 15040 AN: 25662

East Asian (EAS) AF: 0.534 AC: 20993 AN: 39288

South Asian (SAS) AF: 0.543 AC: 45924 AN: 84618

European-Finnish (FIN) AF: 0.647 AC: 34555 AN: 53376

Middle Eastern (MID) AF: 0.543 AC: 3043 AN: 5606

European-Non Finnish (NFE) AF: 0.588 AC: 610880 AN: 1038942

Other (OTH) AF: 0.590 AC: 34001 AN: 57650

GnomAD4 genome AF: 0.647 AC: 98376 AN: 152142 Hom.: 32418 Cov.: 33 AF XY: 0.648 AC XY: 48193 AN XY: 74378

African (AFR) AF: 0.775 AC: 32167 AN: 41526

American (AMR) AF: 0.649 AC: 9923 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2048 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2640 AN: 5160

South Asian (SAS) AF: 0.542 AC: 2614 AN: 4824

European-Finnish (FIN) AF: 0.655 AC: 6932 AN: 10586

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39926 AN: 67978

Other (OTH) AF: 0.638 AC: 1348 AN: 2112

Alfa AF: 0.617 Hom.: 6153

Bravo AF: 0.652

Asia WGS AF: 0.578 AC: 2013 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis imperfecta type 17 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.79
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		-0.085
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: rs1978707; hg19: chr5-151052659; COSMIC: COSV50558545; COSMIC: COSV50558545;