rs865429

Variant summary

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

The NM_025237.3(SOST):​c.220+675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,178 control chromosomes in the GnomAD database, including 51,356 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 0.81 ( 51356 hom., cov: 32)

Consequence

SOST
NM_025237.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813
Variant links:
Genes affected
SOST (HGNC:13771): (sclerostin) Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Loss-of-function mutations in this gene are associated with an autosomal-recessive disorder, sclerosteosis, which causes progressive bone overgrowth. A deletion downstream of this gene, which causes reduced sclerostin expression, is associated with a milder form of the disorder called van Buchem disease. [provided by RefSeq, Jul 2008]

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=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOSTNM_025237.3 linkuse as main transcriptc.220+675C>T intron_variant ENST00000301691.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOSTENST00000301691.3 linkuse as main transcriptc.220+675C>T intron_variant 1 NM_025237.3 P1Q9BQB4-1

Frequencies

GnomAD3 genomes
AF:
0.815
AC:
123886
AN:
152060
Hom.:
51318
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.650
Gnomad AMI
AF:
0.931
Gnomad AMR
AF:
0.876
Gnomad ASJ
AF:
0.844
Gnomad EAS
AF:
0.754
Gnomad SAS
AF:
0.857
Gnomad FIN
AF:
0.928
Gnomad MID
AF:
0.804
Gnomad NFE
AF:
0.882
Gnomad OTH
AF:
0.816
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.815
AC:
123975
AN:
152178
Hom.:
51356
Cov.:
32
AF XY:
0.819
AC XY:
60980
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.650
Gnomad4 AMR
AF:
0.875
Gnomad4 ASJ
AF:
0.844
Gnomad4 EAS
AF:
0.754
Gnomad4 SAS
AF:
0.857
Gnomad4 FIN
AF:
0.928
Gnomad4 NFE
AF:
0.882
Gnomad4 OTH
AF:
0.818
Alfa
AF:
0.870
Hom.:
75962
Bravo
AF:
0.799
Asia WGS
AF:
0.810
AC:
2820
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.030
DANN
Benign
0.57

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: rs865429; hg19: chr17-41835215; API