rs2869678

Positions:

• chr4-87512728-G-A

Variant summary

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

The NM_004684.6(SPARCL1):​c.-11-13143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,044 control chromosomes in the GnomAD database, including 3,583 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 0.21 (3583 hom., cov: 32)
• Consequence: SPARCL1 NM_004684.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.-11-13143C>T		intron_variant		ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.-113-7805C>T		intron_variant			NP_001121782.1
SPARCL1	NM_001291976.2	c.-495-13143C>T		intron_variant			NP_001278905.1
SPARCL1	NM_001291977.2	c.-142+3560C>T		intron_variant			NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.-11-13143C>T		intron_variant		1	NM_004684.6	ENSP00000282470.6

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32590 AN: 151926 Hom.: 3583 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32606 AN: 152044 Hom.: 3583 Cov.: 32 AF XY: 0.213 AC XY: 15827 AN XY: 74312

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.212

Alfa AF: 0.222 Hom.: 5281

Bravo AF: 0.211

Asia WGS AF: 0.186 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.53

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: rs2869678; hg19: chr4-88433880;