4-87529944-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509407.5(SPARCL1):​c.-68-843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 134,230 control chromosomes in the GnomAD database, including 1,569 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 0.15 (1569 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

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>A		intron_variant	Intron 1 of 4	4		ENSP00000423483.1
SPARCL1	ENST00000512317.5	c.-69+601G>A		intron_variant	Intron 2 of 5	4		ENSP00000423448.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 20456 AN: 134124 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0108

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.153 AC: 20473 AN: 134230 Hom.: 1569 Cov.: 32 AF XY: 0.157 AC XY: 10207 AN XY: 64904

African (AFR) AF: 0.103 AC: 3662 AN: 35654

American (AMR) AF: 0.246 AC: 3201 AN: 13000

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 476 AN: 3222

East Asian (EAS) AF: 0.320 AC: 1257 AN: 3928

South Asian (SAS) AF: 0.283 AC: 1092 AN: 3852

European-Finnish (FIN) AF: 0.129 AC: 1160 AN: 8960

Middle Eastern (MID) AF: 0.180 AC: 49 AN: 272

European-Non Finnish (NFE) AF: 0.148 AC: 9258 AN: 62746

Other (OTH) AF: 0.167 AC: 310 AN: 1858

Alfa AF: 0.133 Hom.: 1928

Bravo AF: 0.137

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.6
DANN	Benign	0.42
PhyloP100		-0.35
PromoterAI		0.022	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;