11-9049559-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SCUBE2NM_001367977.2 linkc.1639+1047T>C intron_variant ENST00000649792.2 NP_001354906.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCUBE2ENST00000649792.2 linkc.1639+1047T>C intron_variant NM_001367977.2 ENSP00000497523.1 A0A3B3ISZ7

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10840166; hg19: chr11-9071106; API