rs35681285

Variant names:

• chr7-16287021-T-C
• rs35681285
• NM_001101426.4:c.836-8795A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-16287021-T-C
• chr7-16287021-T-G

Variant summary

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

The NM_001101426.4(CRPPA):​c.836-8795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,276 control chromosomes in the GnomAD database, including 673 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 0.075 (673 hom., cov: 32)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.836-8795A>G		intron_variant	Intron 5 of 9	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001368197.1	c.731-8795A>G		intron_variant	Intron 4 of 8		NP_001355126.1
CRPPA	NM_001101417.4	c.686-8795A>G		intron_variant	Intron 4 of 8		NP_001094887.1
CRPPA	NR_160656.1	n.901-8795A>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.836-8795A>G		intron_variant	Intron 5 of 9	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11421 AN: 152158 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0769

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

GnomAD4 genome AF: 0.0751 AC: 11443 AN: 152276 Hom.: 673 Cov.: 32 AF XY: 0.0732 AC XY: 5448 AN XY: 74454

African (AFR) AF: 0.163 AC: 6754 AN: 41542

American (AMR) AF: 0.0528 AC: 807 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3468

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5182

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4818

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2559 AN: 68028

Other (OTH) AF: 0.0775 AC: 164 AN: 2116

Alfa AF: 0.0514 Hom.: 1271

Bravo AF: 0.0816

Asia WGS AF: 0.0430 AC: 151 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs35681285; hg19: chr7-16326646;