7-16088412-C-CTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001101426.4(CRPPA):c.*3282_*3283insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3161 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.953

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.*3282_*3283insAA		3_prime_UTR_variant	10/10	ENST00000407010.7
CRPPA	NM_001101417.4	c.*3282_*3283insAA		3_prime_UTR_variant	9/9
CRPPA	NM_001368197.1	c.*3282_*3283insAA		3_prime_UTR_variant	9/9
CRPPA	NR_160656.1	n.4703_4704insAA		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.*3282_*3283insAA		3_prime_UTR_variant	10/10	5	NM_001101426.4	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 23735 AN: 110462 Hom.: 3162 Cov.: 0

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.230

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.215 AC: 23722 AN: 110468 Hom.: 3161 Cov.: 0 AF XY: 0.202 AC XY: 10343 AN XY: 51166

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.228

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital Muscular Dystrophy, alpha-dystroglycan related Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71549971; hg19: chr7-16128037;