rs373134516

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001101426.4(CRPPA):c.1246C>T(p.Pro416Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,582,926 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 5 hom. )

Consequence

CRPPA
NM_001101426.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.299

Publications

0 publications found

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

CRPPA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077709556).

BP6

Variant 7-16216071-G-A is Benign according to our data. Variant chr7-16216071-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 289346.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000331 (474/1430740) while in subpopulation SAS AF = 0.0037 (299/80890). AF 95% confidence interval is 0.00335. There are 5 homozygotes in GnomAdExome4. There are 291 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4 link	c.1246C>T	p.Pro416Ser	missense_variant	Exon 9 of 10	ENST00000407010.7	NP_001094896.1	A4D126-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7 link	c.1246C>T	p.Pro416Ser	missense_variant	Exon 9 of 10	5	NM_001101426.4	ENSP00000385478.2		A4D126-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000530

AC:

121

AN:

228200

AF XY:

0.000662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000749

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.000331

AC:

474

AN:

1430740

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

291

AN XY:

712014

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31634

American (AMR)

AF:

0.00

AC:

AN:

38534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24798

East Asian (EAS)

AF:

0.00

AC:

AN:

39200

South Asian (SAS)

AF:

0.00370

AC:

299

AN:

80890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.000141

AC:

155

AN:

1098270

Other (OTH)

AF:

0.000322

AC:

AN:

59016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000164

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00249

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000918

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000278

AC:

ESP6500EA

AF:

0.000369

AC:

ExAC

AF:

0.000629

AC:

Asia WGS

AF:

0.00145

AC:

AN:

3468

EpiCase

AF:

0.00

EpiControl

AF:

0.000120

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 12, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

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

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.3

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.00032

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.3

L;.

PhyloP100

0.30

PrimateAI

Benign

0.28

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.15

Sift

Benign

0.83

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.0010

B;.

Vest4

0.15

MVP

0.29

MPC

0.055

ClinPred

0.016

GERP RS

-0.081

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

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

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rs373134516

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over