rs185594460

Positions:

• chr7-16258455-G-C
• chr7-16258455-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001101426.4(CRPPA):​c.1054C>G​(p.Gln352Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q352K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780

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-AS1 (HGNC:48962): (CRPPA antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043578655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.1054C>G	p.Gln352Glu	missense_variant	8/10	ENST00000407010.7
CRPPA-AS1	NR_038947.1	n.241-7772G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.1054C>G	p.Gln352Glu	missense_variant	8/10	5	NM_001101426.4	P1
CRPPA-AS1	ENST00000438573.5	n.222-3444G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.8
DANN	Benign	0.96
DEOGEN2	Benign	0.0017	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.086
Sift	Benign	0.28	T;T
Sift4G	Benign	0.95	T;T
Polyphen		0.0070	B;.
Vest4		0.15
MutPred		0.26		Gain of solvent accessibility (P = 9e-04);.;
MVP		0.40
MPC		0.059
ClinPred		0.051	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16298080;