rs5759224

Positions:

• chr22-43235073-A-G

Variant summary

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

The NM_173050.5(SCUBE1):​c.845-3198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,254 control chromosomes in the GnomAD database, including 475 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 0.073 (475 hom., cov: 32)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

Genes affected

SCUBE1 (HGNC:13441): (signal peptide, CUB domain and EGF like domain containing 1) This gene encodes a cell surface glycoprotein that is a member of the SCUBE (signal peptide, CUB domain, EGF (epidermal growth factor)-like protein) family. Family members have an amino-terminal signal peptide, nine copies of EGF-like repeats and a CUB domain at the carboxyl terminus. This protein is expressed in platelets and endothelial cells and may play an important role in vascular biology. [provided by RefSeq, Oct 2011]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCUBE1	NM_173050.5	c.845-3198T>C		intron_variant		ENST00000360835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCUBE1	ENST00000360835.9	c.845-3198T>C		intron_variant		1	NM_173050.5	P1
	ENST00000419643.1	n.575+1449A>G		intron_variant, non_coding_transcript_variant		3
SCUBE1	ENST00000449304.5	c.405-3198T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11099 AN: 152136 Hom.: 475 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0721

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

GnomAD4 genome AF: 0.0729 AC: 11105 AN: 152254 Hom.: 475 Cov.: 32 AF XY: 0.0708 AC XY: 5274 AN XY: 74458

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0696 Hom.: 47

Bravo AF: 0.0737

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.40

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: rs5759224; hg19: chr22-43631079;