rs16878759

Variant names:

• chr7-16463459-T-C
• rs16878759
• NM_015464.3:c.206-496A>G

Variant summary

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

The NM_015464.3(SOSTDC1):​c.206-496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 152,324 control chromosomes in the GnomAD database, including 37 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 0.016 (37 hom., cov: 33)
• Consequence: SOSTDC1 NM_015464.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 3 publications found

Genes affected

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]

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]

CRPPA Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• myopathy caused by variation in CRPPA

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2U

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000272537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015464.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOSTDC1	NM_015464.3	MANE Select	c.206-496A>G		intron	N/A	NP_056279.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOSTDC1	ENST00000307068.5	TSL:1 MANE Select	c.206-496A>G		intron	N/A	ENSP00000304930.4
	CRPPA	ENST00000675257.1		c.-47+32921A>G		intron	N/A	ENSP00000501664.1
	CRPPA	ENST00000674759.1		c.-47+32921A>G		intron	N/A	ENSP00000502749.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2454 AN: 152206 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0161 AC: 2456 AN: 152324 Hom.: 37 Cov.: 33 AF XY: 0.0169 AC XY: 1259 AN XY: 74474

African (AFR) AF: 0.00707 AC: 294 AN: 41586

American (AMR) AF: 0.0100 AC: 153 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.0889 AC: 462 AN: 5194

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4822

European-Finnish (FIN) AF: 0.0285 AC: 302 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1076 AN: 68028

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0155 Hom.: 5

Bravo AF: 0.0155

Asia WGS AF: 0.0570 AC: 197 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16878759; hg19: chr7-16503084;