rs2986671

Positions:

• chr9-110430375-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_153366.4(SVEP1):​c.5429A>C​(p.Glu1810Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,612,688 control chromosomes in the GnomAD database, including 28,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2264 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26278 hom.)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

Genes affected

SVEP1 (HGNC:15985): (sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1) Predicted to enable calcium ion binding activity and chromatin binding activity. Predicted to be involved in epidermis development and lymph vessel morphogenesis. Predicted to act upstream of or within several processes, including Tie signaling pathway; lymph circulation; and lymph vessel development. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019336492).
• BP6: Variant 9-110430375-T-G is Benign according to our data. Variant chr9-110430375-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.5429A>C	p.Glu1810Ala	missense_variant	33/48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.5429A>C	p.Glu1810Ala	missense_variant	33/48	5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22674 AN: 151984 Hom.: 2255 Cov.: 32

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.204 AC: 50527 AN: 247354 Hom.: 6319 AF XY: 0.199 AC XY: 26646 AN XY: 134120

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.432

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.180 AC: 263454 AN: 1460586 Hom.: 26278 Cov.: 33 AF XY: 0.179 AC XY: 130027 AN XY: 726466

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.149 AC: 22696 AN: 152102 Hom.: 2264 Cov.: 32 AF XY: 0.156 AC XY: 11567 AN XY: 74334

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.161

Alfa AF: 0.174 Hom.: 4384

Bravo AF: 0.148

TwinsUK AF: 0.175 AC: 650

ALSPAC AF: 0.172 AC: 661

ESP6500AA AF: 0.0365 AC: 137

ESP6500EA AF: 0.170 AC: 1400

ExAC AF: 0.197 AC: 23774

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.63
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T;T
MetaRNN	Benign	0.019	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.65	.;N
PrimateAI	Benign	0.27	T
REVEL	Benign	0.090
Sift4G	Benign	0.092	T;T
Polyphen		0.0040	.;B
Vest4		0.071
MPC		0.10
ClinPred		0.0060	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2986671; hg19: chr9-113192655; COSMIC: COSV52837027;