chr22-43213754-G-A

Position:

• chr22-43213754-G-A

Variant summary

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

The NM_173050.5(SCUBE1):​c.2053+336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 196,718 control chromosomes in the GnomAD database, including 1,929 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 0.14 (1547 hom., cov: 33)
  • Exomes 𝑓: 0.12 (382 hom.)
• Consequence: SCUBE1 NM_173050.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE1	NM_173050.5	c.2053+336C>T		intron_variant		ENST00000360835.9	NP_766638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCUBE1	ENST00000360835.9	c.2053+336C>T		intron_variant		1	NM_173050.5	ENSP00000354080	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21052 AN: 148230 Hom.: 1545 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.117 AC: 5643 AN: 48376 Hom.: 382 AF XY: 0.118 AC XY: 2892 AN XY: 24476

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0701

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0789

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.142 AC: 21056 AN: 148342 Hom.: 1547 Cov.: 33 AF XY: 0.142 AC XY: 10271 AN XY: 72558

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.142

Alfa AF: 0.136 Hom.: 1887

Bravo AF: 0.137

Asia WGS AF: 0.152 AC: 526 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	0.78
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2071725; hg19: chr22-43609760;