7-16308637-AAACAACAAC-AAACAACAACAAC

Variant names:

• chr7-16308637-A-AAAC
• rs142647500
• NM_001101426.4:c.685-13_685-11dupGTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001101426.4(CRPPA):​c.685-13_685-11dupGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,406,232 control chromosomes in the GnomAD database, including 1,186 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (237 hom., cov: 32)
  • Exomes 𝑓: 0.024 (949 hom.)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.808
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 7-16308637-A-AAAC is Benign according to our data. Variant chr7-16308637-A-AAAC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.685-13_685-11dupGTT		intron	N/A	NP_001094896.1	A4D126-1
	CRPPA	NM_001368197.1		c.685-7174_685-7172dupGTT		intron	N/A	NP_001355126.1
	CRPPA	NM_001101417.4		c.535-13_535-11dupGTT		intron	N/A	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.685-11_685-10insGTT		intron	N/A	ENSP00000385478.2	A4D126-1
	CRPPA	ENST00000399310.3	TSL:1	c.535-11_535-10insGTT		intron	N/A	ENSP00000382249.3	A4D126-2
	CRPPA	ENST00000856526.1		c.685-11_685-10insGTT		intron	N/A	ENSP00000526585.1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6820 AN: 152162 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.0423 AC: 9287 AN: 219382 AF XY: 0.0395

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.0678

Gnomad ASJ exome AF: 0.0519

Gnomad EAS exome AF: 0.157

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0241 AC: 30186 AN: 1253954 Hom.: 949 Cov.: 18 AF XY: 0.0244 AC XY: 15420 AN XY: 633132

African (AFR) AF: 0.0559 AC: 1594 AN: 28498

American (AMR) AF: 0.0660 AC: 2776 AN: 42072

Ashkenazi Jewish (ASJ) AF: 0.0515 AC: 1267 AN: 24606

East Asian (EAS) AF: 0.179 AC: 6766 AN: 37884

South Asian (SAS) AF: 0.0329 AC: 2612 AN: 79484

European-Finnish (FIN) AF: 0.0249 AC: 1313 AN: 52742

Middle Eastern (MID) AF: 0.0177 AC: 96 AN: 5420

European-Non Finnish (NFE) AF: 0.0130 AC: 12071 AN: 930110

Other (OTH) AF: 0.0318 AC: 1691 AN: 53138

GnomAD4 genome AF: 0.0449 AC: 6836 AN: 152278 Hom.: 237 Cov.: 32 AF XY: 0.0462 AC XY: 3443 AN XY: 74448

African (AFR) AF: 0.0698 AC: 2900 AN: 41558

American (AMR) AF: 0.0606 AC: 927 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.155 AC: 803 AN: 5164

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4826

European-Finnish (FIN) AF: 0.0266 AC: 282 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1367 AN: 68030

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0160 Hom.: 12

Bravo AF: 0.0507

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs142647500; hg19: chr7-16348262; COSMIC: COSV107504476;