rs5759224

Variant names:

• chr22-43235073-A-G
• rs5759224
• NM_173050.5:c.845-3198T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000234892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.845-3198T>C		intron_variant	Intron 7 of 21	ENST00000360835.9	NP_766638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.845-3198T>C		intron_variant	Intron 7 of 21	1	NM_173050.5	ENSP00000354080.3
SCUBE1	ENST00000449304.5	c.404-3198T>C		intron_variant	Intron 4 of 4	5		ENSP00000395327.1
ENSG00000234892	ENST00000419643.1	n.575+1449A>G		intron_variant	Intron 2 of 2	3

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

African (AFR) AF: 0.114 AC: 4728 AN: 41528

American (AMR) AF: 0.0484 AC: 740 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.0286 AC: 148 AN: 5176

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4826

European-Finnish (FIN) AF: 0.0525 AC: 558 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4420 AN: 68014

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

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
PhyloP100		0.28
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: rs5759224; hg19: chr22-43631079;