7-16088412-CTT-C

Variant names:

• chr7-16088412-CTT-C
• rs71549971
• NM_001101426.4:c.*3281_*3282delAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001101426.4(CRPPA):​c.*3281_*3282delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• 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 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• myopathy caused by variation in CRPPA

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2U

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00226 (256/113108) while in subpopulation AFR AF = 0.00865 (239/27628). AF 95% confidence interval is 0.00775. There are 1 homozygotes in GnomAd4. There are 124 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.*3281_*3282delAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000407010.7	NP_001094896.1
CRPPA	NR_160656.1	n.4702_4703delAA		non_coding_transcript_exon_variant	Exon 8 of 8
CRPPA	NM_001368197.1	c.*3281_*3282delAA		3_prime_UTR_variant	Exon 9 of 9		NP_001355126.1
CRPPA	NM_001101417.4	c.*3281_*3282delAA		3_prime_UTR_variant	Exon 9 of 9		NP_001094887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.*3281_*3282delAA		3_prime_UTR_variant	Exon 10 of 10	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 255 AN: 113116 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00863

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

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: 0.00

Gnomad OTH AF: 0.00259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00226 AC: 256 AN: 113108 Hom.: 1 Cov.: 0 AF XY: 0.00236 AC XY: 124 AN XY: 52514

African (AFR) AF: 0.00865 AC: 239 AN: 27628

American (AMR) AF: 0.00137 AC: 13 AN: 9500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2936

East Asian (EAS) AF: 0.00 AC: 0 AN: 3686

South Asian (SAS) AF: 0.00 AC: 0 AN: 3812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58560

Other (OTH) AF: 0.00257 AC: 4 AN: 1554

Alfa AF: 0.00 Hom.: 201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.95

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

Other links and lift over

dbSNP: rs71549971; hg19: chr7-16128037;