11-9020784-G-T

Variant names:

• chr11-9020784-G-T
• rs1136966
• NM_001367977.2:c.*261C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367977.2(SCUBE2):​c.*261C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 299,716 control chromosomes in the GnomAD database, including 87,474 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 0.76 (44708 hom., cov: 32)
  • Exomes 𝑓: 0.76 (42766 hom.)
• Consequence: SCUBE2 NM_001367977.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• 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]

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE2	NM_001367977.2	c.*261C>A		3_prime_UTR_variant	Exon 23 of 23	ENST00000649792.2	NP_001354906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE2	ENST00000649792.2	c.*261C>A		3_prime_UTR_variant	Exon 23 of 23		NM_001367977.2	ENSP00000497523.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116149 AN: 152060 Hom.: 44658 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.755 AC: 111447 AN: 147538 Hom.: 42766 Cov.: 3 AF XY: 0.753 AC XY: 56688 AN XY: 75282

African (AFR) AF: 0.790 AC: 3855 AN: 4880

American (AMR) AF: 0.762 AC: 3412 AN: 4478

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 3615 AN: 5872

East Asian (EAS) AF: 1.00 AC: 11567 AN: 11572

South Asian (SAS) AF: 0.786 AC: 3561 AN: 4530

European-Finnish (FIN) AF: 0.755 AC: 7310 AN: 9686

Middle Eastern (MID) AF: 0.603 AC: 473 AN: 784

European-Non Finnish (NFE) AF: 0.733 AC: 70188 AN: 95724

Other (OTH) AF: 0.746 AC: 7466 AN: 10012

GnomAD4 genome AF: 0.764 AC: 116253 AN: 152178 Hom.: 44708 Cov.: 32 AF XY: 0.765 AC XY: 56914 AN XY: 74382

African (AFR) AF: 0.793 AC: 32904 AN: 41518

American (AMR) AF: 0.759 AC: 11601 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2112 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5175 AN: 5184

South Asian (SAS) AF: 0.802 AC: 3865 AN: 4822

European-Finnish (FIN) AF: 0.745 AC: 7871 AN: 10568

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50384 AN: 68004

Other (OTH) AF: 0.726 AC: 1531 AN: 2110

Alfa AF: 0.736 Hom.: 68120

Bravo AF: 0.767

Asia WGS AF: 0.905 AC: 3144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.72
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1136966; hg19: chr11-9042331;