rs2528467

Variant names:

• chr7-16479964-G-A
• rs2528467
• ENST00000675257.1:c.-47+16416C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-16479964-G-A
• chr7-16479964-G-C
• chr7-16479964-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396652.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000675257.1		c.-47+16416C>T		intron	N/A	ENSP00000501664.1	A0A6Q8PF75
	CRPPA	ENST00000674759.1		c.-47+16416C>T		intron	N/A	ENSP00000502749.1	A0A6Q8PHI3
	SOSTDC1	ENST00000396652.1	TSL:2	c.-189-14107C>T		intron	N/A	ENSP00000379889.1	Q6X4U4-2

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

African (AFR) AF: 0.108 AC: 4477 AN: 41510

American (AMR) AF: 0.259 AC: 3958 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1088 AN: 5182

South Asian (SAS) AF: 0.364 AC: 1750 AN: 4814

European-Finnish (FIN) AF: 0.303 AC: 3201 AN: 10562

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19160 AN: 67972

Other (OTH) AF: 0.241 AC: 510 AN: 2112

Alfa AF: 0.261 Hom.: 14070

Bravo AF: 0.224

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.9
DANN	Benign	0.64
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2528467;

hg19: chr7-16519589;