9-110496872-T-G

Variant names:

• chr9-110496872-T-G
• rs10817033
• NM_153366.4:c.1743A>C

Variant summary

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

The NM_153366.4(SVEP1):​c.1743A>C​(p.Gln581His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,557,606 control chromosomes in the GnomAD database, including 10,783 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1441 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9342 hom.)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014695525).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.1743A>C	p.Gln581His	missense_variant	Exon 8 of 48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.1743A>C	p.Gln581His	missense_variant	Exon 8 of 48	5	NM_153366.4	ENSP00000363593.2
SVEP1	ENST00000374461.1	c.1743A>C	p.Gln581His	missense_variant	Exon 8 of 14	1		ENSP00000363585.2
SVEP1	ENST00000467821.1	n.1162A>C		non_coding_transcript_exon_variant	Exon 7 of 26	2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19724 AN: 152128 Hom.: 1440 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.0962 AC: 16293 AN: 169348 AF XY: 0.0948

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0705

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.000895

Gnomad FIN exome AF: 0.0907

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.109 AC: 153445 AN: 1405360 Hom.: 9342 Cov.: 31 AF XY: 0.108 AC XY: 74944 AN XY: 693612

African (AFR) AF: 0.203 AC: 6542 AN: 32254

American (AMR) AF: 0.0772 AC: 2805 AN: 36316

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4515 AN: 25256

East Asian (EAS) AF: 0.000514 AC: 19 AN: 36992

South Asian (SAS) AF: 0.0494 AC: 3934 AN: 79658

European-Finnish (FIN) AF: 0.0892 AC: 4441 AN: 49806

Middle Eastern (MID) AF: 0.202 AC: 1154 AN: 5702

European-Non Finnish (NFE) AF: 0.114 AC: 123221 AN: 1081122

Other (OTH) AF: 0.117 AC: 6814 AN: 58254

GnomAD4 genome AF: 0.130 AC: 19731 AN: 152246 Hom.: 1441 Cov.: 32 AF XY: 0.126 AC XY: 9380 AN XY: 74436

African (AFR) AF: 0.193 AC: 8024 AN: 41536

American (AMR) AF: 0.108 AC: 1646 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.0410 AC: 198 AN: 4830

European-Finnish (FIN) AF: 0.0910 AC: 965 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7781 AN: 68012

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.121 Hom.: 3752

Bravo AF: 0.137

TwinsUK AF: 0.106 AC: 392

ALSPAC AF: 0.109 AC: 419

ESP6500AA AF: 0.181 AC: 687

ESP6500EA AF: 0.116 AC: 951

ExAC AF: 0.0703 AC: 7776

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.69	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;M;M
PhyloP100		-0.0020
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D;.;.
Sift4G	Pathogenic	0.0010	D;D;D
Vest4		0.055
ClinPred		0.067	T
GERP RS		0.97
Varity_R		0.49
gMVP		0.33
Mutation Taster		=96/4	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: rs10817033; hg19: chr9-113259152; COSMIC: COSV57029490;