22-43228759-T-C

Variant names:

• chr22-43228759-T-C
• rs139014
• NM_173050.5:c.1084+313A>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.1084+313A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,118 control chromosomes in the GnomAD database, including 2,940 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 0.19 (2940 hom., cov: 33)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.1084+313A>G		intron_variant	Intron 9 of 21	ENST00000360835.9	NP_766638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.1084+313A>G		intron_variant	Intron 9 of 21	1	NM_173050.5	ENSP00000354080.3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28845 AN: 152000 Hom.: 2935 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.190 AC: 28874 AN: 152118 Hom.: 2940 Cov.: 33 AF XY: 0.186 AC XY: 13856 AN XY: 74370

African (AFR) AF: 0.245 AC: 10150 AN: 41484

American (AMR) AF: 0.128 AC: 1964 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.0653 AC: 337 AN: 5162

South Asian (SAS) AF: 0.185 AC: 892 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12905 AN: 67994

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.184 Hom.: 2853

Bravo AF: 0.189

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.29
PhyloP100		-0.94
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: rs139014; hg19: chr22-43624765; COSMIC: COSV62616482; COSMIC: COSV62616482;