7-16088412-CTTTTTTTTTTTTT-CTTTTTT

Variant names:

• chr7-16088412-CTTTTTTT-C
• rs71549971
• NM_001101426.4:c.*3276_*3282delAAAAAAA

Variant summary

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

The NM_001101426.4(CRPPA):​c.*3276_*3282delAAAAAAA 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 0.0038 (1 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• 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 sas. GnomAd4 allele frequency = 0.00378 (427/113110) while in subpopulation SAS AF = 0.00446 (17/3812). AF 95% confidence interval is 0.00285. There are 1 homozygotes in GnomAd4. There are 250 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.*3276_*3282delAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000407010.7	NP_001094896.1
CRPPA	NR_160656.1	n.4697_4703delAAAAAAA		non_coding_transcript_exon_variant	Exon 8 of 8
CRPPA	NM_001368197.1	c.*3276_*3282delAAAAAAA		3_prime_UTR_variant	Exon 9 of 9		NP_001355126.1
CRPPA	NM_001101417.4	c.*3276_*3282delAAAAAAA		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.*3276_*3282delAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 428 AN: 113118 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00954

Gnomad EAS AF: 0.00324

Gnomad SAS AF: 0.00469

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00518

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

GnomAD4 genome AF: 0.00378 AC: 427 AN: 113110 Hom.: 1 Cov.: 0 AF XY: 0.00476 AC XY: 250 AN XY: 52522

African (AFR) AF: 0.000615 AC: 17 AN: 27654

American (AMR) AF: 0.00263 AC: 25 AN: 9498

Ashkenazi Jewish (ASJ) AF: 0.00954 AC: 28 AN: 2934

East Asian (EAS) AF: 0.00298 AC: 11 AN: 3686

South Asian (SAS) AF: 0.00446 AC: 17 AN: 3812

European-Finnish (FIN) AF: 0.0293 AC: 131 AN: 4474

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

European-Non Finnish (NFE) AF: 0.00323 AC: 189 AN: 58548

Other (OTH) AF: 0.00579 AC: 9 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		1.1
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71549971; hg19: chr7-16128037;