5-151663423-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003118.4(SPARC):c.*148T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 768,866 control chromosomes in the GnomAD database, including 600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (103 hom., cov: 33)
  • Exomes 𝑓: 0.036 (497 hom.)
• Consequence: SPARC NM_003118.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.985

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=-0.69).
• BP6: Variant 5-151663423-A-T is Benign according to our data. Variant chr5-151663423-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0282 (4293/152286) while in subpopulation NFE AF= 0.0438 (2982/68024). AF 95% confidence interval is 0.0425. There are 103 homozygotes in gnomad4. There are 2047 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 103 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARC	NM_003118.4	c.*148T>A		3_prime_UTR_variant	10/10	ENST00000231061.9
SPARC	NM_001309443.2	c.*148T>A		3_prime_UTR_variant	10/10
SPARC	NM_001309444.2	c.*32T>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARC	ENST00000231061.9	c.*148T>A		3_prime_UTR_variant	10/10	1	NM_003118.4	P1
SPARC	ENST00000520687.1	n.663T>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4294 AN: 152170 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.0361 AC: 22237 AN: 616580 Hom.: 497 Cov.: 8 AF XY: 0.0354 AC XY: 11485 AN XY: 324210

Gnomad4 AFR exome AF: 0.00728

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.0000291

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.0445

Gnomad4 NFE exome AF: 0.0448

Gnomad4 OTH exome AF: 0.0328

GnomAD4 genome AF: 0.0282 AC: 4293 AN: 152286 Hom.: 103 Cov.: 33 AF XY: 0.0275 AC XY: 2047 AN XY: 74452

Gnomad4 AFR AF: 0.00871

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0331 Hom.: 12

Bravo AF: 0.0254

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	1.0
Dann	Benign	0.87

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: rs1060151; hg19: chr5-151042984;