7-16088412-CTTTTTTTT-C

Variant names:

• chr7-16088412-CTTTTTTTT-C
• rs71549971
• NM_001101426.4:c.*3275_*3282delAAAAAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001101426.4(CRPPA):​c.*3275_*3282delAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (7439 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-16088412-CTTTTTTTT-C is Benign according to our data. Variant chr7-16088412-CTTTTTTTT-C is described in ClinVar as Benign. ClinVar VariationId is 359494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	NM_001101426.4	MANE Select	c.*3275_*3282delAAAAAAAA		3_prime_UTR	Exon 10 of 10	NP_001094896.1	A4D126-1
	CRPPA	NM_001368197.1		c.*3275_*3282delAAAAAAAA		3_prime_UTR	Exon 9 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.*3275_*3282delAAAAAAAA		3_prime_UTR	Exon 9 of 9	NP_001094887.1	A0A140VJM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.*3275_*3282delAAAAAAAA		3_prime_UTR	Exon 10 of 10	ENSP00000385478.2	A4D126-1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 42444 AN: 113208 Hom.: 7435 Cov.: 0

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.489

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.375 AC: 42424 AN: 113192 Hom.: 7439 Cov.: 0 AF XY: 0.384 AC XY: 20170 AN XY: 52580

African (AFR) AF: 0.165 AC: 4567 AN: 27660

American (AMR) AF: 0.445 AC: 4243 AN: 9534

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 810 AN: 2944

East Asian (EAS) AF: 0.391 AC: 1436 AN: 3672

South Asian (SAS) AF: 0.593 AC: 2260 AN: 3810

European-Finnish (FIN) AF: 0.566 AC: 2576 AN: 4548

Middle Eastern (MID) AF: 0.494 AC: 85 AN: 172

European-Non Finnish (NFE) AF: 0.438 AC: 25650 AN: 58532

Other (OTH) AF: 0.367 AC: 566 AN: 1542

Alfa AF: 0.193 Hom.: 201

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71549971; hg19: chr7-16128037;