Variant chr22-43210206-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173050.5(SCUBE1):c.2418C>T(p.Thr806=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,584,144 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

SCUBE1
NM_173050.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-43210206-G-A is Benign according to our data. Variant chr22-43210206-G-A is described in ClinVar as [Benign]. Clinvar id is 711047.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.17 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCUBE1	NM_173050.5 linkuse as main transcript	c.2418C>T	p.Thr806=	synonymous_variant	19/22	ENST00000360835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCUBE1	ENST00000360835.9 linkuse as main transcript	c.2418C>T	p.Thr806=	synonymous_variant	19/22	1	NM_173050.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

401

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000915

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00283

AC:

634

AN:

224134

Hom.:

AF XY:

0.00287

AC XY:

347

AN XY:

120956

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.000915

Gnomad ASJ exome

AF:

0.00371

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00271

GnomAD4 exome

AF:

0.00348

AC:

4977

AN:

1431806

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

2488

AN XY:

709634

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.000834

Gnomad4 ASJ exome

AF:

0.00362

Gnomad4 EAS exome

AF:

0.0000768

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00400

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152338

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.67

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over