NM_173050.5:c.485-340A>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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]

LOC124905129 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.0808 AC: 3354 AN: 41522

American (AMR) AF: 0.289 AC: 4415 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1859 AN: 5150

South Asian (SAS) AF: 0.217 AC: 1042 AN: 4808

European-Finnish (FIN) AF: 0.183 AC: 1938 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11214 AN: 67962

Other (OTH) AF: 0.204 AC: 430 AN: 2112

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
PhyloP100		-1.6
PromoterAI		0.0040	Neutral
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: rs5759236; hg19: chr22-43659191;