rs78374272

chr7-16216016-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001101426.4(CRPPA):c.1251+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,421,782 control chromosomes in the GnomAD database, including 221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (104 hom.)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.629

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]

CRPPA-AS1 (HGNC:48962): (CRPPA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-16216016-T-C is Benign according to our data. Variant chr7-16216016-T-C is described in ClinVar as [Benign]. Clinvar id is 257462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.1251+50A>G		intron_variant		ENST00000407010.7
CRPPA-AS1	NR_038947.1	n.118+5413T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.1251+50A>G		intron_variant		5	NM_001101426.4	P1
CRPPA-AS1	ENST00000438573.5	n.116+5413T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3632 AN: 152170 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00786 AC: 1414 AN: 179860 Hom.: 37 AF XY: 0.00601 AC XY: 583 AN XY: 96934

Gnomad AFR exome AF: 0.0791

Gnomad AMR exome AF: 0.00649

Gnomad ASJ exome AF: 0.000426

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.000340

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00432

GnomAD4 exome AF: 0.00321 AC: 4075 AN: 1269494 Hom.: 104 Cov.: 17 AF XY: 0.00299 AC XY: 1892 AN XY: 633134

Gnomad4 AFR exome AF: 0.0842

Gnomad4 AMR exome AF: 0.00652

Gnomad4 ASJ exome AF: 0.000795

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000515

Gnomad4 FIN exome AF: 0.000321

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.00630

GnomAD4 genome AF: 0.0238 AC: 3632 AN: 152288 Hom.: 117 Cov.: 33 AF XY: 0.0224 AC XY: 1668 AN XY: 74482

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0111 Hom.: 12

Bravo AF: 0.0276

Asia WGS AF: 0.00434 AC: 15 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.29
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78374272; hg19: chr7-16255641;