rs183141256

Variant names:

• chr7-16406235-G-A
• rs183141256
• NM_001101426.4:c.360C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-16406235-G-A
• chr7-16406235-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001101426.4(CRPPA):​c.360C>T​(p.Val120Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V120V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: CRPPA NM_001101426.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -2.10
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-16406235-G-A is Benign according to our data. Variant chr7-16406235-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 288817.
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	NM_001101426.4	MANE Select	c.360C>T	p.Val120Val	synonymous	Exon 2 of 10	NP_001094896.1
	CRPPA	NM_001368197.1		c.360C>T	p.Val120Val	synonymous	Exon 2 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.360C>T	p.Val120Val	synonymous	Exon 2 of 9	NP_001094887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.360C>T	p.Val120Val	synonymous	Exon 2 of 10	ENSP00000385478.2
	CRPPA	ENST00000399310.3	TSL:1	c.360C>T	p.Val120Val	synonymous	Exon 2 of 9	ENSP00000382249.3
	CRPPA	ENST00000676325.1		c.57C>T	p.Val19Val	synonymous	Exon 3 of 11	ENSP00000502074.1

Frequencies

GnomAD3 genomes AF: 0.000888 AC: 135 AN: 152008 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000481

GnomAD2 exomes AF: 0.000277 AC: 69 AN: 249068 AF XY: 0.000207

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000896 AC: 131 AN: 1461654 Hom.: 0 Cov.: 33 AF XY: 0.0000784 AC XY: 57 AN XY: 727106

African (AFR) AF: 0.00311 AC: 104 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111858

Other (OTH) AF: 0.000199 AC: 12 AN: 60374

GnomAD4 genome AF: 0.000907 AC: 138 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.000887 AC XY: 66 AN XY: 74368

African (AFR) AF: 0.00328 AC: 136 AN: 41504

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000542 Hom.: 0

Bravo AF: 0.00115

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	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)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.051
DANN	Benign	0.66
PhyloP100		-2.1

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: rs183141256; hg19: chr7-16445860; COSMIC: COSV104708313;