rs1049544

Variant names:

• chr4-87494484-G-C
• rs1049544
• NM_004684.6:c.316C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-87494484-G-C
• chr4-87494484-G-T

Variant summary

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

The ENST00000282470.11(SPARCL1):​c.316C>G​(p.His106Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,613,206 control chromosomes in the GnomAD database, including 141,115 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H106N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.51 (22766 hom., cov: 32)
  • Exomes 𝑓: 0.39 (118349 hom.)
• Consequence: SPARCL1 ENST00000282470.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 33 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 (MetaRNN=1.3043638E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000282470.11. 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.316C>G	p.His106Asp	missense	Exon 4 of 11	NP_004675.3
	SPARCL1	NM_001128310.3		c.316C>G	p.His106Asp	missense	Exon 5 of 12	NP_001121782.1
	SPARCL1	NM_001291976.2		c.-60C>G		5_prime_UTR	Exon 5 of 12	NP_001278905.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	ENST00000282470.11	TSL:1 MANE Select	c.316C>G	p.His106Asp	missense	Exon 4 of 11	ENSP00000282470.6
	SPARCL1	ENST00000418378.5	TSL:5	c.316C>G	p.His106Asp	missense	Exon 5 of 12	ENSP00000414856.1
	SPARCL1	ENST00000509407.5	TSL:4	c.316C>G	p.His106Asp	missense	Exon 5 of 5	ENSP00000423483.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77841 AN: 151774 Hom.: 22723 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.450 AC: 112968 AN: 251110 AF XY: 0.445

Gnomad AFR exome AF: 0.820

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.431

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.392 AC: 573160 AN: 1461314 Hom.: 118349 Cov.: 39 AF XY: 0.396 AC XY: 288175 AN XY: 726958

African (AFR) AF: 0.820 AC: 27458 AN: 33468

American (AMR) AF: 0.494 AC: 22073 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11768 AN: 26130

East Asian (EAS) AF: 0.395 AC: 15697 AN: 39690

South Asian (SAS) AF: 0.563 AC: 48530 AN: 86234

European-Finnish (FIN) AF: 0.384 AC: 20505 AN: 53398

Middle Eastern (MID) AF: 0.512 AC: 2951 AN: 5766

European-Non Finnish (NFE) AF: 0.358 AC: 398272 AN: 1111532

Other (OTH) AF: 0.429 AC: 25906 AN: 60378

GnomAD4 genome AF: 0.513 AC: 77938 AN: 151892 Hom.: 22766 Cov.: 32 AF XY: 0.515 AC XY: 38219 AN XY: 74212

African (AFR) AF: 0.805 AC: 33354 AN: 41430

American (AMR) AF: 0.496 AC: 7563 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1568 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2173 AN: 5146

South Asian (SAS) AF: 0.571 AC: 2741 AN: 4802

European-Finnish (FIN) AF: 0.395 AC: 4163 AN: 10532

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24600 AN: 67948

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.372 Hom.: 7968

Bravo AF: 0.531

TwinsUK AF: 0.357 AC: 1322

ALSPAC AF: 0.357 AC: 1377

ESP6500AA AF: 0.807 AC: 3557

ESP6500EA AF: 0.372 AC: 3197

ExAC AF: 0.457 AC: 55430

Asia WGS AF: 0.566 AC: 1967 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.40
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.54
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.11
ClinPred		0.0025	T
GERP RS		4.3
Varity_R		0.051
gMVP		0.026
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1049544; hg19: chr4-88415636; COSMIC: COSV56802379; COSMIC: COSV56802379;