22-43239567-T-C

Variant names:

• chr22-43239567-T-C
• rs5751452
• NM_173050.5:c.728-613A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173050.5(SCUBE1):​c.728-613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 152,346 control chromosomes in the GnomAD database, including 712 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 0.055 (712 hom., cov: 34)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173050.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE1	NM_173050.5	MANE Select	c.728-613A>G		intron	N/A	NP_766638.2	Q8IWY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE1	ENST00000360835.9	TSL:1 MANE Select	c.728-613A>G		intron	N/A	ENSP00000354080.3	Q8IWY4
	SCUBE1	ENST00000290460.7	TSL:1	c.818-613A>G		intron	N/A	ENSP00000290460.7	B1AH90
	SCUBE1	ENST00000911327.1		c.665-613A>G		intron	N/A	ENSP00000581386.1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8328 AN: 152228 Hom.: 712 Cov.: 34

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0546 AC: 8315 AN: 152346 Hom.: 712 Cov.: 34 AF XY: 0.0589 AC XY: 4389 AN XY: 74488

African (AFR) AF: 0.0111 AC: 462 AN: 41600

American (AMR) AF: 0.0210 AC: 322 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2229 AN: 5164

South Asian (SAS) AF: 0.125 AC: 602 AN: 4824

European-Finnish (FIN) AF: 0.0855 AC: 908 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0526 AC: 3582 AN: 68040

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0525 Hom.: 150

Bravo AF: 0.0468

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.3
DANN	Benign	0.79
PhyloP100		1.5
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: rs5751452; hg19: chr22-43635573;