rs1049544

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004684.6(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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (22766 hom., cov: 32)
  • Exomes 𝑓: 0.39 (118349 hom.)
• Consequence: SPARCL1 NM_004684.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPARCL1	NM_004684.6	c.316C>G	p.His106Asp	missense_variant	4/11	ENST00000282470.11
SPARCL1	NM_001128310.3	c.316C>G	p.His106Asp	missense_variant	5/12
SPARCL1	NM_001291976.2	c.-60C>G		5_prime_UTR_variant	5/12
SPARCL1	NM_001291977.2	c.-60C>G		5_prime_UTR_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARCL1	ENST00000282470.11	c.316C>G	p.His106Asp	missense_variant	4/11	1	NM_004684.6	P2

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

GnomAD3 exomes AF: 0.450 AC: 112968 AN: 251110 Hom.: 27347 AF XY: 0.445 AC XY: 60415 AN XY: 135704

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 SAS exome AF: 0.565

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

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.429

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

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.495

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 v4.3

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;T;.;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00021	N
MetaRNN	Benign	0.0000013	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.8	N;N;.;.;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.6	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;.;.;.;T
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.025
MPC		0.11
ClinPred		0.0025	T
GERP RS		4.3
Varity_R		0.051
gMVP		0.026

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049544; hg19: chr4-88415636; COSMIC: COSV56802379; COSMIC: COSV56802379;