rs963167

Positions:

• chr11-9090011-A-G
• chr11-9090011-A-T

Variant summary

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

The NM_001367977.2(SCUBE2):​c.134-182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 151,920 control chromosomes in the GnomAD database, including 55,658 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 0.86 (55658 hom., cov: 30)
• Consequence: SCUBE2 NM_001367977.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

SCUBE2 (HGNC:30425): (signal peptide, CUB domain and EGF like domain containing 2) Predicted to enable calcium ion binding activity; hedgehog family protein binding activity; and lipid binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within several processes, including positive regulation of chondrocyte proliferation; positive regulation of osteoblast differentiation; and positive regulation of smoothened signaling pathway. Predicted to be located in extracellular region. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE2	NM_001367977.2	c.134-182T>C		intron_variant		ENST00000649792.2	NP_001354906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCUBE2	ENST00000649792.2	c.134-182T>C		intron_variant			NM_001367977.2	ENSP00000497523	P1
	ENST00000663085.1	n.592A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129851 AN: 151802 Hom.: 55612 Cov.: 30

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.855 AC: 129944 AN: 151920 Hom.: 55658 Cov.: 30 AF XY: 0.852 AC XY: 63214 AN XY: 74218

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.830

Alfa AF: 0.866 Hom.: 27199

Bravo AF: 0.858

Asia WGS AF: 0.752 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.34

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: rs963167; hg19: chr11-9111558;