7-16460517-A-G

Variant names:

• chr7-16460517-A-G
• rs10270805
• ENST00000675257.1:c.-47+35863T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000675257.1(CRPPA):​c.-47+35863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,114 control chromosomes in the GnomAD database, including 65,762 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (65762 hom., cov: 31)
• Consequence: CRPPA ENST00000675257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 7 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

ENSG00000272537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675257.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000675257.1		c.-47+35863T>C		intron	N/A	ENSP00000501664.1	A0A6Q8PF75
	CRPPA	ENST00000674759.1		c.-47+35863T>C		intron	N/A	ENSP00000502749.1	A0A6Q8PHI3
	ENSG00000272537	ENST00000605985.2	TSL:6	n.565-643A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141249 AN: 151996 Hom.: 65710 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.929 AC: 141361 AN: 152114 Hom.: 65762 Cov.: 31 AF XY: 0.932 AC XY: 69268 AN XY: 74360

African (AFR) AF: 0.941 AC: 39033 AN: 41494

American (AMR) AF: 0.947 AC: 14457 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2804 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5176

South Asian (SAS) AF: 0.871 AC: 4198 AN: 4822

European-Finnish (FIN) AF: 0.966 AC: 10237 AN: 10596

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62441 AN: 67968

Other (OTH) AF: 0.918 AC: 1934 AN: 2106

Alfa AF: 0.917 Hom.: 188117

Bravo AF: 0.930

Asia WGS AF: 0.932 AC: 3240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.81
PhyloP100		-0.0040

Splicing

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

Other links and lift over

dbSNP: rs10270805; hg19: chr7-16500142;