chr22-43239567-T-C

Position:

• chr22-43239567-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.728-613A>G		intron_variant		ENST00000360835.9	NP_766638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.728-613A>G		intron_variant		1	NM_173050.5	ENSP00000354080	P1
SCUBE1	ENST00000290460.7	c.818-613A>G		intron_variant		1		ENSP00000290460
SCUBE1	ENST00000449304.5	c.288-613A>G		intron_variant		5		ENSP00000395327

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

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0855

Gnomad4 NFE AF: 0.0526

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0484 Hom.: 69

Bravo AF: 0.0468

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.3
DANN	Benign	0.79

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: rs5751452; hg19: chr22-43635573;