rs1889321

Positions:

• chr9-110538555-C-T

Variant summary

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

The NM_153366.4(SVEP1):​c.964+7560G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,950 control chromosomes in the GnomAD database, including 36,801 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 0.69 (36801 hom., cov: 33)
• Consequence: SVEP1 NM_153366.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.964+7560G>A		intron_variant		ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.964+7560G>A		intron_variant		5	NM_153366.4	ENSP00000363593	P1
SVEP1	ENST00000374461.1	c.964+7560G>A		intron_variant		1		ENSP00000363585
SVEP1	ENST00000467821.1	n.383+7560G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104469 AN: 151832 Hom.: 36805 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.688 AC: 104502 AN: 151950 Hom.: 36801 Cov.: 33 AF XY: 0.684 AC XY: 50859 AN XY: 74302

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.690

Alfa AF: 0.725 Hom.: 81486

Bravo AF: 0.693

Asia WGS AF: 0.455 AC: 1585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.76

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: rs1889321; hg19: chr9-113300835;