rs16878689

chr7-16091661-G-Achr7-16091661-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_001101426.4(CRPPA):c.*34C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,190,706 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.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00135 (206/152196) while in subpopulation AFR AF= 0.00486 (202/41538). AF 95% confidence interval is 0.00431. There are 0 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.*34C>T		3_prime_UTR_variant	10/10	ENST00000407010.7
CRPPA	NM_001101417.4	c.*34C>T		3_prime_UTR_variant	9/9
CRPPA	NM_001368197.1	c.*34C>T		3_prime_UTR_variant	9/9
CRPPA	NR_160656.1	n.1455C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.*34C>T		3_prime_UTR_variant	10/10	5	NM_001101426.4	P1
CRPPA	ENST00000399310.3	c.*34C>T		3_prime_UTR_variant	9/9	1
CRPPA	ENST00000675257.1	c.*34C>T		3_prime_UTR_variant	10/10
CRPPA	ENST00000676325.1	c.*34C>T		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152078 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000339 AC: 50 AN: 147588 Hom.: 0 AF XY: 0.000296 AC XY: 23 AN XY: 77756

Gnomad AFR exome AF: 0.00535

Gnomad AMR exome AF: 0.000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000974

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000108 AC: 112 AN: 1038510 Hom.: 0 Cov.: 13 AF XY: 0.000102 AC XY: 54 AN XY: 527722

Gnomad4 AFR exome AF: 0.00384

Gnomad4 AMR exome AF: 0.000274

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000296

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000216

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.00122 AC XY: 91 AN XY: 74386

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000113 Hom.: 41

Bravo AF: 0.00155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs16878689; hg19: chr7-16131286;