11-9090011-A-G

Variant names:

• chr11-9090011-A-G
• rs963167
• NM_001367977.2:c.134-182T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000286935 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367977.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE2	NM_001367977.2	MANE Select	c.134-182T>C		intron	N/A	NP_001354906.1
	SCUBE2	NM_001330199.3		c.134-182T>C		intron	N/A	NP_001317128.1
	SCUBE2	NM_020974.4		c.134-182T>C		intron	N/A	NP_066025.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE2	ENST00000649792.2	MANE Select	c.134-182T>C		intron	N/A	ENSP00000497523.1
	SCUBE2	ENST00000450649.6	TSL:1	c.134-182T>C		intron	N/A	ENSP00000415187.2
	ENSG00000286935	ENST00000663085.1		n.592A>G		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.842 AC: 34894 AN: 41420

American (AMR) AF: 0.841 AC: 12831 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2775 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4179 AN: 5148

South Asian (SAS) AF: 0.811 AC: 3903 AN: 4814

European-Finnish (FIN) AF: 0.840 AC: 8844 AN: 10524

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59657 AN: 67976

Other (OTH) AF: 0.830 AC: 1754 AN: 2112

Alfa AF: 0.869 Hom.: 115627

Bravo AF: 0.858

Asia WGS AF: 0.752 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.34
PhyloP100		-1.2
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: rs963167; hg19: chr11-9111558;