rs139478143

Variant names:

• chr7-16258873-CAT-C
• rs139478143
• NM_001101426.4:c.1026+45_1026+46delAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001101426.4(CRPPA):​c.1026+45_1026+46delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,194,472 control chromosomes in the GnomAD database, including 10,114 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (798 hom., cov: 31)
  • Exomes 𝑓: 0.13 (9316 hom.)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34

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 -16 ACMG points.

• BP6: Variant 7-16258873-CAT-C is Benign according to our data. Variant chr7-16258873-CAT-C is described in ClinVar as [Benign]. Clinvar id is 257461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.1026+45_1026+46delAT		intron_variant	Intron 7 of 9	ENST00000407010.7	NP_001094896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.1026+45_1026+46delAT		intron_variant	Intron 7 of 9	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13803 AN: 151968 Hom.: 798 Cov.: 31

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.112 AC: 20027 AN: 179064 Hom.: 1336 AF XY: 0.120 AC XY: 11518 AN XY: 96382

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.0733

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.0955

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.128 AC: 133735 AN: 1042386 Hom.: 9316 AF XY: 0.130 AC XY: 69187 AN XY: 531696

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.0494

Gnomad4 ASJ exome AF: 0.0695

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0983

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.0907 AC: 13794 AN: 152086 Hom.: 798 Cov.: 31 AF XY: 0.0903 AC XY: 6714 AN XY: 74344

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0955

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.108

Alfa AF: 0.102 Hom.: 172

Bravo AF: 0.0863

Asia WGS AF: 0.109 AC: 376 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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: rs139478143; hg19: chr7-16298498;