NM_015464.3:c.206-573G>A

Variant names:

• chr7-16463536-C-T
• rs17619769
• NM_015464.3:c.206-573G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015464.3(SOSTDC1):​c.206-573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,146 control chromosomes in the GnomAD database, including 3,190 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 0.19 (3190 hom., cov: 33)
• Consequence: SOSTDC1 NM_015464.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 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.206-573G>A		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.206-573G>A		intron	N/A	ENSP00000304930.4
	CRPPA	ENST00000675257.1		c.-47+32844G>A		intron	N/A	ENSP00000501664.1
	CRPPA	ENST00000674759.1		c.-47+32844G>A		intron	N/A	ENSP00000502749.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28503 AN: 152028 Hom.: 3194 Cov.: 33

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.187 AC: 28508 AN: 152146 Hom.: 3190 Cov.: 33 AF XY: 0.192 AC XY: 14305 AN XY: 74362

African (AFR) AF: 0.0675 AC: 2805 AN: 41528

American (AMR) AF: 0.239 AC: 3654 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5178

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4820

European-Finnish (FIN) AF: 0.288 AC: 3044 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15768 AN: 67980

Other (OTH) AF: 0.186 AC: 394 AN: 2114

Alfa AF: 0.176 Hom.: 924

Bravo AF: 0.178

Asia WGS AF: 0.183 AC: 638 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		0.82
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: rs17619769; hg19: chr7-16503161;