rs2528467

Variant summary

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

The ENST00000396652.1(SOSTDC1):​c.-189-14107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,108 control chromosomes in the GnomAD database, including 4,815 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 0.23 ( 4815 hom., cov: 33)

Consequence

SOSTDC1
ENST00000396652.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.456
Variant links:
Genes affected
CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
use as main transcriptn.16479964G>A intergenic_region

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRPPAENST00000675257.1 linkuse as main transcriptc.-47+16416C>T intron_variant ENSP00000501664.1 A0A6Q8PF75
CRPPAENST00000674759.1 linkuse as main transcriptc.-47+16416C>T intron_variant ENSP00000502749.1 A0A6Q8PHI3
SOSTDC1ENST00000396652.1 linkuse as main transcriptc.-189-14107C>T intron_variant 2 ENSP00000379889.1 Q6X4U4-2

Frequencies

GnomAD3 genomes
AF:
0.235
AC:
35708
AN:
151990
Hom.:
4823
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.204
Gnomad AMR
AF:
0.259
Gnomad ASJ
AF:
0.376
Gnomad EAS
AF:
0.209
Gnomad SAS
AF:
0.363
Gnomad FIN
AF:
0.303
Gnomad MID
AF:
0.288
Gnomad NFE
AF:
0.282
Gnomad OTH
AF:
0.243
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.235
AC:
35716
AN:
152108
Hom.:
4815
Cov.:
33
AF XY:
0.241
AC XY:
17901
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.108
Gnomad4 AMR
AF:
0.259
Gnomad4 ASJ
AF:
0.376
Gnomad4 EAS
AF:
0.210
Gnomad4 SAS
AF:
0.364
Gnomad4 FIN
AF:
0.303
Gnomad4 NFE
AF:
0.282
Gnomad4 OTH
AF:
0.241
Alfa
AF:
0.272
Hom.:
5375
Bravo
AF:
0.224
Asia WGS
AF:
0.258
AC:
899
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
8.9
DANN
Benign
0.64

Splicing

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: rs2528467; hg19: chr7-16519589; API