rs6959787

Variant names:

• chr7-16490077-A-G
• rs6959787
• ENST00000675257.1:c.-47+6303T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.9).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000675257.1	c.-47+6303T>C		intron_variant	Intron 2 of 9			ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-47+6303T>C		intron_variant	Intron 2 of 9			ENSP00000502749.1
SOSTDC1	ENST00000396652.1	c.-190+6303T>C		intron_variant	Intron 2 of 4	2		ENSP00000379889.1

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

African (AFR) AF: 0.530 AC: 21953 AN: 41426

American (AMR) AF: 0.436 AC: 6650 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3021 AN: 5164

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4818

European-Finnish (FIN) AF: 0.434 AC: 4556 AN: 10504

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27800 AN: 67952

Other (OTH) AF: 0.462 AC: 971 AN: 2104

Alfa AF: 0.441 Hom.: 1916

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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6959787; hg19: chr7-16529702;