rs1049539

Positions:

• chr4-87529196-T-C

Variant summary

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

The NM_004684.6(SPARCL1):​c.-163A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,144 control chromosomes in the GnomAD database, including 7,336 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 0.30 (7336 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SPARCL1 NM_004684.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

Genes affected

SPARCL1 (HGNC:11220): (SPARC like 1) Predicted to enable calcium ion binding activity; collagen binding activity; and extracellular matrix binding activity. Predicted to be involved in anatomical structure development and regulation of synapse organization. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.-163A>G		5_prime_UTR_variant	1/11	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.-265A>G		5_prime_UTR_variant	1/12		NP_001121782.1
SPARCL1	NM_001291976.2	c.-647A>G		5_prime_UTR_variant	1/12		NP_001278905.1
SPARCL1	NM_001291977.2	c.-298A>G		5_prime_UTR_variant	1/10		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.-163A>G		5_prime_UTR_variant	1/11	1	NM_004684.6	ENSP00000282470	P2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44922 AN: 152022 Hom.: 7323 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.296 AC: 44973 AN: 152140 Hom.: 7336 Cov.: 32 AF XY: 0.302 AC XY: 22441 AN XY: 74378

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.286

Alfa AF: 0.234 Hom.: 4302

Bravo AF: 0.305

Asia WGS AF: 0.372 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.86

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: rs1049539; hg19: chr4-88450348; COSMIC: COSV56803367; COSMIC: COSV56803367;