11-9049559-A-G

Position:

• chr11-9049559-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE2	NM_001367977.2	c.1639+1047T>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.1639+1047T>C		intron_variant			NM_001367977.2	ENSP00000497523.1

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

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.451

Alfa AF: 0.488 Hom.: 22527

Bravo AF: 0.465

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.67

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: rs10840166; hg19: chr11-9071106;