chr4-87517024-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

SPARCL1 Gene-Disease associations (from GenCC):

• corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• stromal corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004684.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	NM_004684.6	MANE Select	c.-12+12021A>G		intron	N/A	NP_004675.3
	SPARCL1	NM_001128310.3		c.-114+12021A>G		intron	N/A	NP_001121782.1	Q14515-1
	SPARCL1	NM_001291976.2		c.-496+12021A>G		intron	N/A	NP_001278905.1	Q14515-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	ENST00000282470.11	TSL:1 MANE Select	c.-12+12021A>G		intron	N/A	ENSP00000282470.6	Q14515-1
	SPARCL1	ENST00000946054.1		c.-12+12021A>G		intron	N/A	ENSP00000616113.1
	SPARCL1	ENST00000880794.1		c.-12+12021A>G		intron	N/A	ENSP00000550853.1

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

African (AFR) AF: 0.660 AC: 27368 AN: 41438

American (AMR) AF: 0.541 AC: 8262 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1871 AN: 3470

East Asian (EAS) AF: 0.757 AC: 3914 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3122 AN: 4802

European-Finnish (FIN) AF: 0.560 AC: 5911 AN: 10562

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31662 AN: 67938

Other (OTH) AF: 0.544 AC: 1150 AN: 2114

Alfa AF: 0.517 Hom.: 3412

Bravo AF: 0.557

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.79
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: rs1965907; hg19: chr4-88438176;