4-87529944-C-G

Variant names:

• chr4-87529944-C-G
• rs17012830
• ENST00000509407.5:c.-68-843G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000509407.5(SPARCL1):​c.-68-843G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 134,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000022 (0 hom., cov: 32)
• Consequence: SPARCL1 ENST00000509407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 1 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):

• stromal corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000509407.5	c.-68-843G>C		intron_variant	Intron 1 of 4	4		ENSP00000423483.1
SPARCL1	ENST00000512317.5	c.-69+601G>C		intron_variant	Intron 2 of 5	4		ENSP00000423448.1

Frequencies

GnomAD3 genomes AF: 0.0000224 AC: 3 AN: 134152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000319

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000224 AC: 3 AN: 134152 Hom.: 0 Cov.: 32 AF XY: 0.0000463 AC XY: 3 AN XY: 64806

African (AFR) AF: 0.0000281 AC: 1 AN: 35558

American (AMR) AF: 0.00 AC: 0 AN: 12988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3224

East Asian (EAS) AF: 0.00 AC: 0 AN: 3938

South Asian (SAS) AF: 0.00 AC: 0 AN: 3852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000319 AC: 2 AN: 62756

Other (OTH) AF: 0.00 AC: 0 AN: 1842

Alfa AF: 0.00 Hom.: 1928

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.38
PhyloP100		-0.35
PromoterAI		0.00090	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17012830; hg19: chr4-88451096;