chr22-43253695-T-C

Variant names:

• chr22-43253695-T-C
• rs139027
• NM_173050.5:c.727+4524A>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.727+4524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 140,678 control chromosomes in the GnomAD database, including 2,757 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 0.20 (2757 hom., cov: 31)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.727+4524A>G		intron_variant	Intron 6 of 21	ENST00000360835.9	NP_766638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.727+4524A>G		intron_variant	Intron 6 of 21	1	NM_173050.5	ENSP00000354080.3
SCUBE1	ENST00000290460.7	c.817+1793A>G		intron_variant	Intron 7 of 7	1		ENSP00000290460.7
SCUBE1	ENST00000449304.5	c.286+1793A>G		intron_variant	Intron 3 of 4	5		ENSP00000395327.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 28210 AN: 140574 Hom.: 2753 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.201 AC: 28240 AN: 140678 Hom.: 2757 Cov.: 31 AF XY: 0.198 AC XY: 13667 AN XY: 68876

African (AFR) AF: 0.179 AC: 5937 AN: 33096

American (AMR) AF: 0.172 AC: 2541 AN: 14780

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 541 AN: 3300

East Asian (EAS) AF: 0.109 AC: 535 AN: 4890

South Asian (SAS) AF: 0.234 AC: 1106 AN: 4736

European-Finnish (FIN) AF: 0.173 AC: 1782 AN: 10304

Middle Eastern (MID) AF: 0.149 AC: 42 AN: 282

European-Non Finnish (NFE) AF: 0.229 AC: 15191 AN: 66432

Other (OTH) AF: 0.196 AC: 393 AN: 2008

Alfa AF: 0.208 Hom.: 3609

Bravo AF: 0.182

Asia WGS AF: 0.156 AC: 539 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	0.35
DANN	Benign	0.43
PhyloP100		-0.46
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: rs139027; hg19: chr22-43649701;