chr7-16308637-AAAC-A

Position:

• chr7-16308637-AAAC-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001101426.4(CRPPA):​c.685-13_685-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,403,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: CRPPA NM_001101426.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.808

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 7-16308637-AAAC-A is Benign according to our data. Variant chr7-16308637-AAAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1680776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-16308637-AAAC-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.685-13_685-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000407010.7	NP_001094896.1
CRPPA	NM_001101417.4	c.535-13_535-11del		splice_polypyrimidine_tract_variant, intron_variant			NP_001094887.1
CRPPA	NM_001368197.1	c.685-7174_685-7172del		intron_variant			NP_001355126.1
CRPPA	NR_160656.1	n.901-30414_901-30412del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.685-13_685-11del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001101426.4	ENSP00000385478	P1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000336 AC: 420 AN: 1251576 Hom.: 0 AF XY: 0.000353 AC XY: 223 AN XY: 631862

Gnomad4 AFR exome AF: 0.000422

Gnomad4 AMR exome AF: 0.0000953

Gnomad4 ASJ exome AF: 0.0000407

Gnomad4 EAS exome AF: 0.00209

Gnomad4 SAS exome AF: 0.000379

Gnomad4 FIN exome AF: 0.0000950

Gnomad4 NFE exome AF: 0.000297

Gnomad4 OTH exome AF: 0.000245

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74326

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000449 Hom.: 12

Bravo AF: 0.000121

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs142647500; hg19: chr7-16348262;