NM_004684.6:c.-11-13143C>T

Variant names:

• chr4-87512728-G-A
• rs2869678
• NM_004684.6:c.-11-13143C>T

Variant summary

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

The NM_004684.6(SPARCL1):​c.-11-13143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,044 control chromosomes in the GnomAD database, including 3,583 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 0.21 (3583 hom., cov: 32)
• Consequence: SPARCL1 NM_004684.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• 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):

• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	NM_004684.6	MANE Select	c.-11-13143C>T		intron	N/A	NP_004675.3
	SPARCL1	NM_001128310.3		c.-113-7805C>T		intron	N/A	NP_001121782.1
	SPARCL1	NM_001291976.2		c.-495-13143C>T		intron	N/A	NP_001278905.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	ENST00000282470.11	TSL:1 MANE Select	c.-11-13143C>T		intron	N/A	ENSP00000282470.6
	SPARCL1	ENST00000946054.1		c.-11-13143C>T		intron	N/A	ENSP00000616113.1
	SPARCL1	ENST00000880794.1		c.-11-13143C>T		intron	N/A	ENSP00000550853.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32590 AN: 151926 Hom.: 3583 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.214 AC: 32606 AN: 152044 Hom.: 3583 Cov.: 32 AF XY: 0.213 AC XY: 15827 AN XY: 74312

African (AFR) AF: 0.216 AC: 8942 AN: 41466

American (AMR) AF: 0.166 AC: 2534 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3468

East Asian (EAS) AF: 0.170 AC: 875 AN: 5162

South Asian (SAS) AF: 0.129 AC: 619 AN: 4814

European-Finnish (FIN) AF: 0.211 AC: 2224 AN: 10564

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15924 AN: 67978

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.222 Hom.: 6686

Bravo AF: 0.211

Asia WGS AF: 0.186 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		0.36
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: rs2869678; hg19: chr4-88433880;