rs10816998

Positions:

• chr9-110371461-A-G

Variant summary

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

The NM_153366.4(SVEP1):​c.10601-1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,914 control chromosomes in the GnomAD database, including 9,199 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 0.34 (9199 hom., cov: 31)
• Consequence: SVEP1 NM_153366.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVEP1	NM_153366.4	c.10601-1445T>C		intron_variant		ENST00000374469.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVEP1	ENST00000374469.6	c.10601-1445T>C		intron_variant		5	NM_153366.4	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52216 AN: 151796 Hom.: 9174 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.344 AC: 52286 AN: 151914 Hom.: 9199 Cov.: 31 AF XY: 0.342 AC XY: 25401 AN XY: 74218

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.340

Alfa AF: 0.320 Hom.: 14382

Bravo AF: 0.350

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0020
DANN	Benign	0.34

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: rs10816998; hg19: chr9-113133741;