chr17-43754075-G-GC

Position:

• chr17-43754075-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025237.3(SOST):​c.*1266_*1267insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19618 hom., cov: 0)
  • Exomes 𝑓: 0.41 (4 hom.)
• Consequence: SOST NM_025237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-43754075-G-GC is Benign according to our data. Variant chr17-43754075-G-GC is described in ClinVar as [Benign]. Clinvar id is 323430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOST	NM_025237.3	c.*1266_*1267insG		3_prime_UTR_variant	2/2	ENST00000301691.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOST	ENST00000301691.3	c.*1266_*1267insG		3_prime_UTR_variant	2/2	1	NM_025237.3	P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75866 AN: 151788 Hom.: 19561 Cov.: 0

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.414 AC: 24 AN: 58 Hom.: 4 Cov.: 0 AF XY: 0.421 AC XY: 16 AN XY: 38

Gnomad4 FIN exome AF: 0.429

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.500 AC: 75982 AN: 151906 Hom.: 19618 Cov.: 0 AF XY: 0.503 AC XY: 37384 AN XY: 74274

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.448

Alfa AF: 0.472 Hom.: 1695

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary bone dysplasia with increased bone density Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs17881550; hg19: chr17-41831443; COSMIC: COSV57012126;