Genetic Variant NM_001101426.4: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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NM_001101426.4:c.3281_3282dupAA

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