7-16421291-G-C

Position:

chr7-16421291-G-C

Variant summary

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

The NM_001101426.4(CRPPA):c.32C>G(p.Pro11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,270,768 control chromosomes in the GnomAD database, including 22 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 0.0068 ( 12 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 10 hom. )

Consequence

CRPPA
NM_001101426.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.869

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=0.0046298504).

BP6

Variant 7-16421291-G-C is Benign according to our data. Variant chr7-16421291-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 129286.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 = 0.00681 (1035/152012) while in subpopulation AFR AF= 0.0242 (1004/41524). AF 95% confidence interval is 0.0229. There are 12 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4 linkuse as main transcript	c.32C>G	p.Pro11Arg	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.32C>G	p.Pro11Arg	missense_variant	1/10	5	NM_001101426.4	ENSP00000385478.2	A4D126-1
CRPPA	ENST00000399310.3 linkuse as main transcript	c.32C>G	p.Pro11Arg	missense_variant	1/9	1		ENSP00000382249.3	A4D126-2
CRPPA	ENST00000675257.1 linkuse as main transcript	c.-46-14954C>G		intron_variant				ENSP00000501664.1	A0A6Q8PF75
CRPPA	ENST00000674759.1 linkuse as main transcript	c.-46-14954C>G		intron_variant				ENSP00000502749.1	A0A6Q8PHI3

Frequencies

GnomAD3 genomes

AF:

0.00679

AC:

1032

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000591

AC:

661

AN:

1118756

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

276

AN XY:

532460

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000718

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000267

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00681

AC:

1035

AN:

152012

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

485

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00765

ExAC

AF:

0.000520

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2018	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. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 15, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 29, 2019	- -

CRPPA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 23, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

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 25, 2024

- -

Congenital Muscular Dystrophy, alpha-dystroglycan related

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0059

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.13

B;.

Vest4

0.18

MVP

0.38

MPC

0.062

ClinPred

0.39

GERP RS

3.0

Varity_R

0.28

gMVP

0.66

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