rs13051

Positions:

• chr4-87495036-G-T

Variant summary

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

The NM_001291976.2(SPARCL1):​c.-230C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,608,716 control chromosomes in the GnomAD database, including 140,871 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 0.51 (22817 hom., cov: 33)
  • Exomes 𝑓: 0.39 (118054 hom.)
• Consequence: SPARCL1 NM_001291976.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951

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=9.185086E-7).
• 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	Protein	UniProt
SPARCL1	NM_004684.6	c.146C>A	p.Ala49Asp	missense_variant	3/11	ENST00000282470.11	NP_004675.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.146C>A	p.Ala49Asp	missense_variant	3/11	1	NM_004684.6	ENSP00000282470.6

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77955 AN: 152022 Hom.: 22774 Cov.: 33

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: 0.449 AC: 112080 AN: 249676 Hom.: 27137 AF XY: 0.444 AC XY: 59942 AN XY: 134954

Gnomad AFR exome AF: 0.820

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.430

Gnomad SAS exome AF: 0.563

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.392 AC: 570514 AN: 1456576 Hom.: 118054 Cov.: 33 AF XY: 0.396 AC XY: 286965 AN XY: 724788

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.562

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.513 AC: 78052 AN: 152140 Hom.: 22817 Cov.: 33 AF XY: 0.515 AC XY: 38305 AN XY: 74374

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.495

Alfa AF: 0.393 Hom.: 19777

Bravo AF: 0.531

TwinsUK AF: 0.357 AC: 1325

ALSPAC AF: 0.357 AC: 1377

ESP6500AA AF: 0.807 AC: 3556

ESP6500EA AF: 0.372 AC: 3196

ExAC AF: 0.457 AC: 55427

Asia WGS AF: 0.567 AC: 1971 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.4
DANN	Benign	0.17
DEOGEN2	Benign	0.019	T;T;.;.;T;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.26	.;T;T;T;T;T;T;T
MetaRNN	Benign	9.2e-7	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N;.;.;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.4	N;N;N;N;N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.93	T;T;T;T;T;T;T;T
Sift4G	Benign	0.74	T;T;.;.;.;T;T;.
Polyphen		0.0	B;B;.;.;.;.;.;.
Vest4		0.038
MPC		0.12
ClinPred		0.00023	T
GERP RS		3.0
Varity_R		0.062
gMVP		0.085

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

Publications

LitVar

Other links and lift over

dbSNP: rs13051; hg19: chr4-88416188; COSMIC: COSV56802387;