Genetic Variant CRPPA:c.*3281_*3282dupAA (chr7-16088412-C-CTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001101426.4(CRPPA):c.*3281_*3282dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.21 ( 3161 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

CRPPA
NM_001101426.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.953

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 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
myopathy caused by variation in CRPPA
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2U
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CRPPA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4 link	c.3281_3282dupAA	3_prime_UTR_variant	Exon 10 of 10	ENST00000407010.7	NP_001094896.1	A4D126-1
CRPPA	NR_160656.1 link	n.4702_4703dupAA	non_coding_transcript_exon_variant	Exon 8 of 8
CRPPA	NM_001368197.1 link	c.3281_3282dupAA	3_prime_UTR_variant	Exon 9 of 9		NP_001355126.1
CRPPA	NM_001101417.4 link	c.3281_3282dupAA	3_prime_UTR_variant	Exon 9 of 9		NP_001094887.1	A4D126-2A0A140VJM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7 link	c.3281_3282dupAA		3_prime_UTR_variant	Exon 10 of 10	5	NM_001101426.4	ENSP00000385478.2		A4D126-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

23735

AN:

110462

Hom.:

3162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.0555

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.181

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.230

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.215

AC:

23722

AN:

110468

Hom.:

3161

Cov.:

AF XY:

0.202

AC XY:

10343

AN XY:

51166

show subpopulations

African (AFR)

AF:

0.0667

AC:

1835

AN:

27506

American (AMR)

AF:

0.242

AC:

2209

AN:

9120

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1042

AN:

2876

East Asian (EAS)

AF:

0.0555

AC:

202

AN:

3642

South Asian (SAS)

AF:

0.112

AC:

417

AN:

3732

European-Finnish (FIN)

AF:

0.131

AC:

545

AN:

4166

Middle Eastern (MID)

AF:

0.177

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.295

AC:

16807

AN:

56978

Other (OTH)

AF:

0.228

AC:

349

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

562

1124

1687

2249

2811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.159

Hom.:

201

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital Muscular Dystrophy, alpha-dystroglycan related

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over