4-87517024-T-C

Variant names:

• chr4-87517024-T-C
• rs1965907
• NM_004684.6:c.-12+12021A>G

Variant summary

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

The NM_004684.6(SPARCL1):​c.-12+12021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,978 control chromosomes in the GnomAD database, including 23,950 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 0.55 (23950 hom., cov: 31)
• Consequence: SPARCL1 NM_004684.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.-12+12021A>G		intron_variant	Intron 1 of 10	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.-114+12021A>G		intron_variant	Intron 1 of 11		NP_001121782.1
SPARCL1	NM_001291976.2	c.-496+12021A>G		intron_variant	Intron 1 of 11		NP_001278905.1
SPARCL1	NM_001291977.2	c.-146-732A>G		intron_variant	Intron 1 of 9		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.-12+12021A>G		intron_variant	Intron 1 of 10	1	NM_004684.6	ENSP00000282470.6

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84013 AN: 151860 Hom.: 23924 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.553 AC: 84083 AN: 151978 Hom.: 23950 Cov.: 31 AF XY: 0.561 AC XY: 41666 AN XY: 74284

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.544

Alfa AF: 0.513 Hom.: 3250

Bravo AF: 0.557

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.52

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: rs1965907; hg19: chr4-88438176;