9-110434983-T-C

Position:

• chr9-110434983-T-C

Variant summary

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

The NM_153366.4(SVEP1):​c.4888+258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,824 control chromosomes in the GnomAD database, including 32,615 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 0.65 (32615 hom., cov: 29)
• Consequence: SVEP1 NM_153366.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.4888+258A>G		intron_variant		ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.4888+258A>G		intron_variant		5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98499 AN: 151708 Hom.: 32582 Cov.: 29

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.649 AC: 98584 AN: 151824 Hom.: 32615 Cov.: 29 AF XY: 0.658 AC XY: 48784 AN XY: 74182

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.624

Alfa AF: 0.656 Hom.: 70535

Bravo AF: 0.650

Asia WGS AF: 0.821 AC: 2853 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.39

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: rs7042161; hg19: chr9-113197263;