11-9049559-A-G

Variant names:

• chr11-9049559-A-G
• rs10840166
• NM_001367977.2:c.1639+1047T>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.1639+1047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,940 control chromosomes in the GnomAD database, including 17,341 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 0.47 (17341 hom., cov: 31)
• Consequence: SCUBE2 NM_001367977.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 4 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]

NRIP3-DT (HGNC:55524): (NRIP3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 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.1639+1047T>C		intron	N/A	NP_001354906.1
	SCUBE2	NM_001330199.3		c.1552+1047T>C		intron	N/A	NP_001317128.1
	SCUBE2	NM_020974.4		c.1639+1047T>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.1639+1047T>C		intron	N/A	ENSP00000497523.1
	SCUBE2	ENST00000450649.6	TSL:1	c.1331-1997T>C		intron	N/A	ENSP00000415187.2
	SCUBE2	ENST00000309263.7	TSL:5	c.1552+1047T>C		intron	N/A	ENSP00000310658.3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71143 AN: 151822 Hom.: 17332 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.468 AC: 71183 AN: 151940 Hom.: 17341 Cov.: 31 AF XY: 0.470 AC XY: 34905 AN XY: 74248

African (AFR) AF: 0.335 AC: 13890 AN: 41442

American (AMR) AF: 0.573 AC: 8755 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3464

East Asian (EAS) AF: 0.439 AC: 2272 AN: 5172

South Asian (SAS) AF: 0.382 AC: 1832 AN: 4802

European-Finnish (FIN) AF: 0.582 AC: 6127 AN: 10530

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35218 AN: 67946

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.492 Hom.: 52353

Bravo AF: 0.465

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		-0.021
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: rs10840166; hg19: chr11-9071106;