rs1327533

Variant names:

• chr9-110368883-T-G
• rs1327533
• NM_153366.4:c.10694+1040A>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.10694+1040A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 151,716 control chromosomes in the GnomAD database, including 630 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 0.084 (630 hom., cov: 32)
• Consequence: SVEP1 NM_153366.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 8 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.10694+1040A>C		intron_variant	Intron 47 of 47	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.10694+1040A>C		intron_variant	Intron 47 of 47	5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12789 AN: 151598 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0448

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0843 AC: 12797 AN: 151716 Hom.: 630 Cov.: 32 AF XY: 0.0863 AC XY: 6406 AN XY: 74188

African (AFR) AF: 0.139 AC: 5778 AN: 41474

American (AMR) AF: 0.0551 AC: 840 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 155 AN: 3458

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5186

South Asian (SAS) AF: 0.0655 AC: 315 AN: 4808

European-Finnish (FIN) AF: 0.107 AC: 1119 AN: 10504

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0631 AC: 4277 AN: 67740

Other (OTH) AF: 0.0769 AC: 162 AN: 2106

Alfa AF: 0.0883 Hom.: 286

Bravo AF: 0.0817

Asia WGS AF: 0.0600 AC: 207 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.79
PhyloP100		1.2
Mutation Taster		=100/0	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: rs1327533; hg19: chr9-113131163;