ENST00000675257.1:c.-176-299C>T

Variant names:

• chr7-16496808-G-A
• rs7801569
• ENST00000675257.1:c.-176-299C>T

Variant summary

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

The ENST00000675257.1(CRPPA):​c.-176-299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,934 control chromosomes in the GnomAD database, including 25,449 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 0.57 (25449 hom., cov: 31)
• Consequence: CRPPA ENST00000675257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675257.1. 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.-176-299C>T		intron	N/A	ENSP00000501664.1
	CRPPA	ENST00000674759.1		c.-176-299C>T		intron	N/A	ENSP00000502749.1
	SOSTDC1	ENST00000396652.1	TSL:2	c.-319-299C>T		intron	N/A	ENSP00000379889.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87192 AN: 151818 Hom.: 25410 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.575 AC: 87294 AN: 151934 Hom.: 25449 Cov.: 31 AF XY: 0.577 AC XY: 42827 AN XY: 74256

African (AFR) AF: 0.642 AC: 26608 AN: 41452

American (AMR) AF: 0.611 AC: 9332 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3470

East Asian (EAS) AF: 0.776 AC: 3984 AN: 5136

South Asian (SAS) AF: 0.517 AC: 2478 AN: 4792

European-Finnish (FIN) AF: 0.575 AC: 6057 AN: 10532

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35082 AN: 67968

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.415 Hom.: 1072

Bravo AF: 0.584

Asia WGS AF: 0.690 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.097
PhyloP100		-2.0
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: rs7801569; hg19: chr7-16536433;