rs6959787

Positions:

• chr7-16490077-A-G

Variant summary

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

The ENST00000675257.1(CRPPA):​c.-47+6303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,896 control chromosomes in the GnomAD database, including 15,921 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 0.45 (15921 hom., cov: 32)
• Consequence: CRPPA ENST00000675257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOSTDC1	ENST00000396652.1	c.-190+6303T>C		intron_variant		2
CRPPA	ENST00000674759.1	c.-47+6303T>C		intron_variant
CRPPA	ENST00000675257.1	c.-47+6303T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68774 AN: 151778 Hom.: 15900 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.453 AC: 68861 AN: 151896 Hom.: 15921 Cov.: 32 AF XY: 0.453 AC XY: 33586 AN XY: 74202

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.462

Alfa AF: 0.436 Hom.: 1791

Bravo AF: 0.459

Asia WGS AF: 0.470 AC: 1629 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6959787; hg19: chr7-16529702;