rs16878759

Positions:

• chr7-16463459-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105375168 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOSTDC1	NM_015464.3	c.206-496A>G		intron_variant		ENST00000307068.5	NP_056279.1
LOC105375168	XR_007060223.1	n.581-7161T>C		intron_variant, non_coding_transcript_variant
LOC105375168	XR_007060220.1	n.736+2143T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOSTDC1	ENST00000307068.5	c.206-496A>G		intron_variant		1	NM_015464.3	ENSP00000304930	P1
SOSTDC1	ENST00000396652.1	c.278-496A>G		intron_variant		2		ENSP00000379889
CRPPA	ENST00000674759.1	c.-47+32921A>G		intron_variant				ENSP00000502749
CRPPA	ENST00000675257.1	c.-47+32921A>G		intron_variant				ENSP00000501664

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

Gnomad4 AFR AF: 0.00707

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0285

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0184

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.71

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: rs16878759; hg19: chr7-16503084;