rs2389591

Variant names:

• chr7-16189817-A-G
• rs2389591
• NM_001101426.4:c.1251+26249T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-16189817-A-G
• chr7-16189817-A-T

Variant summary

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

The NM_001101426.4(CRPPA):​c.1251+26249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,060 control chromosomes in the GnomAD database, including 39,703 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 0.72 (39703 hom., cov: 32)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.1251+26249T>C		intron_variant	Intron 9 of 9	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001368197.1	c.1146+26249T>C		intron_variant	Intron 8 of 8		NP_001355126.1
CRPPA	NM_001101417.4	c.1101+26249T>C		intron_variant	Intron 8 of 8		NP_001094887.1
CRPPA	NR_160656.1	n.1316+26249T>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.1251+26249T>C		intron_variant	Intron 9 of 9	5	NM_001101426.4	ENSP00000385478.2
CRPPA	ENST00000399310.3	c.1101+26249T>C		intron_variant	Intron 8 of 8	1		ENSP00000382249.3
CRPPA	ENST00000676325.1	c.948+26249T>C		intron_variant	Intron 10 of 10			ENSP00000502074.1
CRPPA	ENST00000675257.1	c.843+26249T>C		intron_variant	Intron 9 of 9			ENSP00000501664.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109207 AN: 151942 Hom.: 39655 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.719 AC: 109308 AN: 152060 Hom.: 39703 Cov.: 32 AF XY: 0.723 AC XY: 53754 AN XY: 74318

African (AFR) AF: 0.601 AC: 24925 AN: 41468

American (AMR) AF: 0.793 AC: 12106 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2935 AN: 3468

East Asian (EAS) AF: 0.746 AC: 3856 AN: 5172

South Asian (SAS) AF: 0.749 AC: 3611 AN: 4820

European-Finnish (FIN) AF: 0.779 AC: 8231 AN: 10560

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51138 AN: 67994

Other (OTH) AF: 0.734 AC: 1551 AN: 2114

Alfa AF: 0.742 Hom.: 15238

Bravo AF: 0.715

Asia WGS AF: 0.792 AC: 2748 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.78
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: rs2389591; hg19: chr7-16229442;