rs2528467

Positions:

• chr7-16479964-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000396652.1(SOSTDC1):​c.-189-14107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,108 control chromosomes in the GnomAD database, including 4,815 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 0.23 (4815 hom., cov: 33)
• Consequence: SOSTDC1 ENST00000396652.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

Genes affected

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]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.16479964G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000675257.1	c.-47+16416C>T		intron_variant				ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-47+16416C>T		intron_variant				ENSP00000502749.1
SOSTDC1	ENST00000396652.1	c.-189-14107C>T		intron_variant		2		ENSP00000379889.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35708 AN: 151990 Hom.: 4823 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.235 AC: 35716 AN: 152108 Hom.: 4815 Cov.: 33 AF XY: 0.241 AC XY: 17901 AN XY: 74354

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.241

Alfa AF: 0.272 Hom.: 5375

Bravo AF: 0.224

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.9
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2528467; hg19: chr7-16519589;