rs2389591

Positions:

• chr7-16189817-A-G
• chr7-16189817-A-T

Variant summary

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

The NM_001101426.4(CRPPA):​c.1251+26249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,060 control chromosomes in the GnomAD database, including 39,703 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 0.72 (39703 hom., cov: 32)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.1251+26249T>C		intron_variant		ENST00000407010.7
CRPPA	NM_001101417.4	c.1101+26249T>C		intron_variant
CRPPA	NM_001368197.1	c.1146+26249T>C		intron_variant
CRPPA	NR_160656.1	n.1316+26249T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.1251+26249T>C		intron_variant		5	NM_001101426.4	P1
CRPPA	ENST00000399310.3	c.1101+26249T>C		intron_variant		1
CRPPA	ENST00000675257.1	c.843+26249T>C		intron_variant
CRPPA	ENST00000676325.1	c.948+26249T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109207 AN: 151942 Hom.: 39655 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.719 AC: 109308 AN: 152060 Hom.: 39703 Cov.: 32 AF XY: 0.723 AC XY: 53754 AN XY: 74318

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.734

Alfa AF: 0.741 Hom.: 9358

Bravo AF: 0.715

Asia WGS AF: 0.792 AC: 2748 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.66

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: rs2389591; hg19: chr7-16229442;