7-16216083-G-A

Variant names:

• chr7-16216083-G-A
• rs747967711
• NM_001101426.4:c.1234C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101426.4(CRPPA):​c.1234C>T​(p.Leu412Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L412V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4208241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.1234C>T	p.Leu412Phe	missense_variant	Exon 9 of 10	ENST00000407010.7	NP_001094896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.1234C>T	p.Leu412Phe	missense_variant	Exon 9 of 10	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442952 Hom.: 0 Cov.: 27 AF XY: 0.00000279 AC XY: 2 AN XY: 717882

African (AFR) AF: 0.0000308 AC: 1 AN: 32494

American (AMR) AF: 0.00 AC: 0 AN: 41778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 82720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102740

Other (OTH) AF: 0.00 AC: 0 AN: 59620

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	0.058
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		1.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.036	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.99	D;.
Vest4		0.48
MutPred		0.30		Loss of sheet (P = 0.0817);.;
MVP		0.66
MPC		0.28
ClinPred		0.78	D
GERP RS		2.1
Varity_R		0.17
gMVP		0.41
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs747967711; hg19: chr7-16255708;