rs187484645

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001101426.4(CRPPA):c.67G>T(p.Gly23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,314,636 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

CRPPA
NM_001101426.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.305

Variant links:

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 links:

CRPPA (HGNC:):

CRPPA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007257074).

BP6

Variant 7-16421256-C-A is Benign according to our data. Variant chr7-16421256-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 257463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.003 (456/152084) while in subpopulation AFR AF= 0.00997 (414/41538). AF 95% confidence interval is 0.00917. There are 2 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4 linkuse as main transcript	c.67G>T	p.Gly23Cys	missense_variant	1/10	ENST00000407010.7	NP_001094896.1	A4D126-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRPPA	ENST00000407010.7 linkuse as main transcript	c.67G>T	p.Gly23Cys	missense_variant	1/10	5	NM_001101426.4	ENSP00000385478.2	A4D126-1
CRPPA	ENST00000399310.3 linkuse as main transcript	c.67G>T	p.Gly23Cys	missense_variant	1/9	1		ENSP00000382249.3	A4D126-2
CRPPA	ENST00000675257.1 linkuse as main transcript	c.-46-14919G>T		intron_variant				ENSP00000501664.1	A0A6Q8PF75
CRPPA	ENST00000674759.1 linkuse as main transcript	c.-46-14919G>T		intron_variant				ENSP00000502749.1	A0A6Q8PHI3

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

456

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00997

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.000316

AC:

AN:

15844

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

8196

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000264

AC:

307

AN:

1162552

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

142

AN XY:

558362

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000731

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00300

AC:

456

AN:

152084

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

213

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00997

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00521

Bravo

AF:

0.00341

ExAC

AF:

0.000373

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 08, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 14, 2019	This variant is associated with the following publications: (PMID: 30564623) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0089

T;.

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;.

Vest4

0.26

MVP

0.61

MPC

0.31

ClinPred

0.061

GERP RS

4.0

Varity_R

0.24

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over