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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375168	XR_007060219.1	n.581-643A>G		intron_variant	Intron 4 of 4
LOC105375168	XR_007060220.1	n.580-643A>G		intron_variant	Intron 4 of 5
LOC105375168	XR_007060221.1	n.611-643A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000675257.1	c.-47+35863T>C		intron_variant	Intron 2 of 9			ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-47+35863T>C		intron_variant	Intron 2 of 9			ENSP00000502749.1
ENSG00000272537	ENST00000605985.2	n.565-643A>G		intron_variant	Intron 4 of 5	6
ENSG00000272537	ENST00000780753.1	n.485+8686A>G		intron_variant	Intron 4 of 4

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 v4.3

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;