7-16287021-T-C

Position:

• chr7-16287021-T-C

Variant summary

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

The NM_001101426.4(CRPPA):​c.836-8795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,276 control chromosomes in the GnomAD database, including 673 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 0.075 (673 hom., cov: 32)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.836-8795A>G		intron_variant		ENST00000407010.7
CRPPA	NM_001101417.4	c.686-8795A>G		intron_variant
CRPPA	NM_001368197.1	c.731-8795A>G		intron_variant
CRPPA	NR_160656.1	n.901-8795A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.836-8795A>G		intron_variant		5	NM_001101426.4	P1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11421 AN: 152158 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0769

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

GnomAD4 genome AF: 0.0751 AC: 11443 AN: 152276 Hom.: 673 Cov.: 32 AF XY: 0.0732 AC XY: 5448 AN XY: 74454

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0775

Alfa AF: 0.0469 Hom.: 477

Bravo AF: 0.0816

Asia WGS AF: 0.0430 AC: 151 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.81

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: rs35681285; hg19: chr7-16326646;