Genetic Variant SCUBE1:c.2053+336C>T (chr22-43213754-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173050.5(SCUBE1):c.2053+336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 196,718 control chromosomes in the GnomAD database, including 1,929 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 0.14 ( 1547 hom., cov: 33)

Exomes 𝑓: 0.12 ( 382 hom. )

Consequence

SCUBE1
NM_173050.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.367

Publications

17 publications found

Variant links:

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]

SCUBE1 links:

SCUBE1-AS2 (HGNC:40633): (SCUBE1 antisense RNA 2)

SCUBE1-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE1	NM_173050.5 link	c.2053+336C>T		intron_variant	Intron 16 of 21	ENST00000360835.9	NP_766638.2	Q8IWY4Q86TI6Q6ZS56A0JP65
SCUBE1-AS2	NR_134632.1 link	n.*93G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9 link	c.2053+336C>T		intron_variant	Intron 16 of 21	1	NM_173050.5	ENSP00000354080.3		Q8IWY4
SCUBE1-AS2	ENST00000420269.1 link	n.*93G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21052

AN:

148230

Hom.:

1545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.148

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.117

AC:

5643

AN:

48376

Hom.:

382

AF XY:

0.118

AC XY:

2892

AN XY:

24476

show subpopulations

African (AFR)

AF:

0.175

AC:

273

AN:

1558

American (AMR)

AF:

0.0803

AC:

133

AN:

1656

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

279

AN:

1954

East Asian (EAS)

AF:

0.0701

AC:

228

AN:

3254

South Asian (SAS)

AF:

0.197

AC:

390

AN:

1980

European-Finnish (FIN)

AF:

0.0789

AC:

238

AN:

3016

Middle Eastern (MID)

AF:

0.150

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.117

AC:

3671

AN:

31362

Other (OTH)

AF:

0.118

AC:

393

AN:

3342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

257

513

770

1026

1283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.142

AC:

21056

AN:

148342

Hom.:

1547

Cov.:

AF XY:

0.142

AC XY:

10271

AN XY:

72558

show subpopulations

African (AFR)

AF:

0.181

AC:

6927

AN:

38172

American (AMR)

AF:

0.107

AC:

1617

AN:

15048

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

528

AN:

3438

East Asian (EAS)

AF:

0.0666

AC:

345

AN:

5184

South Asian (SAS)

AF:

0.222

AC:

1068

AN:

4810

European-Finnish (FIN)

AF:

0.106

AC:

1119

AN:

10590

Middle Eastern (MID)

AF:

0.149

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.132

AC:

8944

AN:

67844

Other (OTH)

AF:

0.142

AC:

293

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

919

1837

2756

3674

4593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

2407

Bravo

AF:

0.137

Asia WGS

AF:

0.152

AC:

526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.78

(source)

DANN

Benign

0.54

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over