7-16463435-C-T

Variant names:

• chr7-16463435-C-T
• rs12699800
• NM_015464.3:c.206-472G>A

Variant summary

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

The NM_015464.3(SOSTDC1):​c.206-472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,784 control chromosomes in the GnomAD database, including 20,630 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 0.50 (20630 hom., cov: 32)
• Consequence: SOSTDC1 NM_015464.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOSTDC1	NM_015464.3	MANE Select	c.206-472G>A		intron	N/A	NP_056279.1	Q6X4U4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOSTDC1	ENST00000307068.5	TSL:1 MANE Select	c.206-472G>A		intron	N/A	ENSP00000304930.4	Q6X4U4-1
	CRPPA	ENST00000675257.1		c.-47+32945G>A		intron	N/A	ENSP00000501664.1	A0A6Q8PF75
	CRPPA	ENST00000674759.1		c.-47+32945G>A		intron	N/A	ENSP00000502749.1	A0A6Q8PHI3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76175 AN: 151666 Hom.: 20626 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.502 AC: 76212 AN: 151784 Hom.: 20630 Cov.: 32 AF XY: 0.497 AC XY: 36873 AN XY: 74172

African (AFR) AF: 0.298 AC: 12339 AN: 41352

American (AMR) AF: 0.558 AC: 8518 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3462

East Asian (EAS) AF: 0.424 AC: 2183 AN: 5152

South Asian (SAS) AF: 0.442 AC: 2119 AN: 4796

European-Finnish (FIN) AF: 0.535 AC: 5638 AN: 10532

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41608 AN: 67932

Other (OTH) AF: 0.520 AC: 1093 AN: 2100

Alfa AF: 0.551 Hom.: 3797

Bravo AF: 0.496

Asia WGS AF: 0.423 AC: 1467 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		0.0040
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

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

Other links and lift over

dbSNP: rs12699800; hg19: chr7-16503060;