Variant chr17-43755022-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025237.3(SOST):c.*320C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 353,596 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 26 hom., cov: 32)

Exomes 𝑓: 0.015 ( 27 hom. )

Consequence

SOST
NM_025237.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

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]

SOST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-43755022-G-A is Benign according to our data. Variant chr17-43755022-G-A is described in ClinVar as [Benign]. Clinvar id is 892296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0128 (1953/152292) while in subpopulation NFE AF= 0.0197 (1337/68010). AF 95% confidence interval is 0.0188. There are 26 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOST	NM_025237.3 linkuse as main transcript	c.*320C>T		3_prime_UTR_variant	2/2	ENST00000301691.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOST	ENST00000301691.3 linkuse as main transcript	c.*320C>T		3_prime_UTR_variant	2/2	1	NM_025237.3	P1	Q9BQB4-1

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1954

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0152

AC:

3053

AN:

201304

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1632

AN XY:

102990

show subpopulations

Gnomad4 AFR exome

AF:

0.00309

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.00198

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0185

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.0180

Gnomad4 OTH exome

AF:

0.0135

GnomAD4 genome

AF:

0.0128

AC:

1953

AN:

152292

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

923

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00339

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0184

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Sclerosteosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.9

DANN

Benign

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over