Genetic Variant NM_001101426.4:c.1251+89T>A (chr7-16215977-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001101426.4(CRPPA):c.1251+89T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,037,554 control chromosomes in the GnomAD database, including 224,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 31397 hom., cov: 32)

Exomes 𝑓: 0.66 ( 192621 hom. )

Consequence

CRPPA
NM_001101426.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.501

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-16215977-A-T is Benign according to our data. Variant chr7-16215977-A-T is described in ClinVar as [Benign]. Clinvar id is 682001.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4 link	c.1251+89T>A		intron_variant	Intron 9 of 9	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.1251+89T>A		intron_variant	Intron 9 of 9	5	NM_001101426.4	ENSP00000385478.2		A4D126-1

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97265

AN:

151942

Hom.:

31358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.625

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.628

GnomAD4 exome

AF:

0.657

AC:

581967

AN:

885494

Hom.:

192621

AF XY:

0.657

AC XY:

295872

AN XY:

450526

show subpopulations

African (AFR)

AF:

0.546

AC:

10826

AN:

19842

American (AMR)

AF:

0.710

AC:

16707

AN:

23532

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

9835

AN:

15954

East Asian (EAS)

AF:

0.481

AC:

16470

AN:

34236

South Asian (SAS)

AF:

0.641

AC:

32708

AN:

51006

European-Finnish (FIN)

AF:

0.732

AC:

33681

AN:

46034

Middle Eastern (MID)

AF:

0.649

AC:

1757

AN:

2708

European-Non Finnish (NFE)

AF:

0.665

AC:

434161

AN:

652514

Other (OTH)

AF:

0.651

AC:

25822

AN:

39668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

9376

18752

28128

37504

46880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.640

AC:

97355

AN:

152060

Hom.:

31397

Cov.:

AF XY:

0.645

AC XY:

47965

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.558

AC:

23109

AN:

41448

American (AMR)

AF:

0.694

AC:

10606

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

2168

AN:

3468

East Asian (EAS)

AF:

0.506

AC:

2612

AN:

5164

South Asian (SAS)

AF:

0.652

AC:

3142

AN:

4820

European-Finnish (FIN)

AF:

0.738

AC:

7804

AN:

10572

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.674

AC:

45827

AN:

67984

Other (OTH)

AF:

0.628

AC:

1328

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1789

3579

5368

7158

8947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.564

Hom.:

1690

Bravo

AF:

0.630

Asia WGS

AF:

0.617

AC:

2134

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

(source)

DANN

Benign

0.69

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism (auto)

(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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NM_001101426.4:c.1251+89T>A

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