chr7-16216071-G-A

Position:

chr7-16216071-G-A

Variant summary

Our verdict is Benign. Variant got -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. 16/20 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

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 made for transcript

Verdict is Benign. Variant got -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. gnomad4_exome 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 gnomad4_exome. There are 291 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4 linkuse as main transcript	c.1246C>T	p.Pro416Ser	missense_variant	9/10	ENST00000407010.7
CRPPA-AS1	NR_038947.1 linkuse as main transcript	n.118+5468G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7 linkuse as main transcript	c.1246C>T	p.Pro416Ser	missense_variant	9/10	5	NM_001101426.4	P1	A4D126-1
CRPPA-AS1	ENST00000438573.5 linkuse as main transcript	n.116+5468G>A		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.000530

AC:

121

AN:

228200

Hom.:

AF XY:

0.000662

AC XY:

AN XY:

123876

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 SAS exome

AF:

0.00438

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

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.000322

GnomAD4 genome

AF:

0.000164

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

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

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 12, 2016

- -

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

Dec 18, 2023

- -

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

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;.

MutationTaster

Benign

1.0

N;N

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

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