rs7782939

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001101426.4(CRPPA):c.55A>C(p.Ser19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,297,340 control chromosomes in the GnomAD database, including 60,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6867 hom., cov: 33)

Exomes 𝑓: 0.30 ( 53827 hom. )

Consequence

CRPPA
NM_001101426.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.69

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:

LOC105375168 (HGNC:):

LOC105375168 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=0.0036817193).

BP6

Variant 7-16421268-T-G is Benign according to our data. Variant chr7-16421268-T-G is described in ClinVar as [Benign]. Clinvar id is 129288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-16421268-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4 link	c.55A>C	p.Ser19Arg	missense_variant	Exon 1 of 10	ENST00000407010.7	NP_001094896.1	A4D126-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRPPA	ENST00000407010.7 link	c.55A>C	p.Ser19Arg	missense_variant	Exon 1 of 10	5	NM_001101426.4	ENSP00000385478.2	A4D126-1
CRPPA	ENST00000399310.3 link	c.55A>C	p.Ser19Arg	missense_variant	Exon 1 of 9	1		ENSP00000382249.3	A4D126-2
CRPPA	ENST00000675257.1 link	c.-46-14931A>C		intron_variant	Intron 2 of 9			ENSP00000501664.1	A0A6Q8PF75
CRPPA	ENST00000674759.1 link	c.-46-14931A>C		intron_variant	Intron 2 of 9			ENSP00000502749.1	A0A6Q8PHI3

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45300

AN:

151428

Hom.:

6873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.257

AC:

3585

AN:

13926

Hom.:

495

AF XY:

0.245

AC XY:

1746

AN XY:

7114

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.304

AC:

348776

AN:

1145802

Hom.:

53827

Cov.:

AF XY:

0.304

AC XY:

166475

AN XY:

548400

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.299

AC:

45311

AN:

151538

Hom.:

6867

Cov.:

AF XY:

0.300

AC XY:

22202

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.291

Hom.:

806

Bravo

AF:

0.296

TwinsUK

AF:

0.317

AC:

1174

ALSPAC

AF:

0.320

AC:

1232

ExAC

AF:

0.119

AC:

1435

Asia WGS

AF:

0.337

AC:

1170

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ser19Arg in exon 1 of ISPD: This variant is not expected to have clinical sign ificance because it has been identified in 39.9% (71/178) of English and Scottis h chromosomes from a broad population by the 1000 Genomes Project (http://www.nc bi.nlm.nih.gov/projects/SNP; dbSNP rs7782939). -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital Muscular Dystrophy, alpha-dystroglycan related

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.4

DANN

Benign

0.79

DEOGEN2

Benign

0.0014

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.14

Sift

Benign

0.88

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;.

Vest4

0.028

MutPred

0.24

Gain of methylation at S19 (P = 0.0183);Gain of methylation at S19 (P = 0.0183);

MPC

0.060

ClinPred

0.0010

GERP RS

-3.6

Varity_R

0.046

gMVP

0.41

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

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