rs5759236

Variant names:

• chr22-43263185-T-A
• rs5759236
• NM_173050.5:c.485-340A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173050.5(SCUBE1):​c.485-340A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,108 control chromosomes in the GnomAD database, including 2,572 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 0.16 (2572 hom., cov: 32)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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]

LOC124905129 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.485-340A>T		intron_variant	Intron 4 of 21	ENST00000360835.9	NP_766638.2
LOC124905129	XR_007068120.1	n.3850T>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.485-340A>T		intron_variant	Intron 4 of 21	1	NM_173050.5	ENSP00000354080.3
SCUBE1	ENST00000290460.7	c.485-340A>T		intron_variant	Intron 4 of 7	1		ENSP00000290460.7

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25043 AN: 151988 Hom.: 2566 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.165 AC: 25044 AN: 152108 Hom.: 2572 Cov.: 32 AF XY: 0.170 AC XY: 12643 AN XY: 74340

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.204

Alfa AF: 0.149 Hom.: 233

Bravo AF: 0.172

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.16
DANN	Benign	0.58

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: rs5759236; hg19: chr22-43659191;