rs4129319

Variant names:

• chr4-87474233-C-T
• rs4129319
• NM_004684.6:c.1967-430G>A

Variant summary

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

The NM_004684.6(SPARCL1):​c.1967-430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,854 control chromosomes in the GnomAD database, including 11,706 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 0.38 (11706 hom., cov: 31)
• Consequence: SPARCL1 NM_004684.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.1967-430G>A		intron_variant	Intron 10 of 10	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.1967-430G>A		intron_variant	Intron 11 of 11		NP_001121782.1
SPARCL1	NM_001291976.2	c.1592-430G>A		intron_variant	Intron 11 of 11		NP_001278905.1
SPARCL1	NM_001291977.2	c.1592-430G>A		intron_variant	Intron 9 of 9		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.1967-430G>A		intron_variant	Intron 10 of 10	1	NM_004684.6	ENSP00000282470.6
SPARCL1	ENST00000418378.5	c.1967-430G>A		intron_variant	Intron 11 of 11	5		ENSP00000414856.1
SPARCL1	ENST00000503414.5	c.1592-430G>A		intron_variant	Intron 11 of 11	2		ENSP00000422903.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57916 AN: 151736 Hom.: 11686 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.382 AC: 57973 AN: 151854 Hom.: 11706 Cov.: 31 AF XY: 0.383 AC XY: 28392 AN XY: 74202

African (AFR) AF: 0.500 AC: 20706 AN: 41394

American (AMR) AF: 0.243 AC: 3712 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3464

East Asian (EAS) AF: 0.484 AC: 2494 AN: 5154

South Asian (SAS) AF: 0.264 AC: 1267 AN: 4806

European-Finnish (FIN) AF: 0.461 AC: 4846 AN: 10520

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22729 AN: 67950

Other (OTH) AF: 0.348 AC: 734 AN: 2108

Alfa AF: 0.335 Hom.: 4937

Bravo AF: 0.375

Asia WGS AF: 0.381 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.33
PhyloP100		0.76
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: rs4129319; hg19: chr4-88395385;