chr7-16102621-A-G

Variant names:

• chr7-16102621-A-G
• rs7798339
• NM_001101426.4:c.1252-10822T>C

Variant summary

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

The NM_001101426.4(CRPPA):​c.1252-10822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 151,798 control chromosomes in the GnomAD database, including 48,457 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 0.79 (48457 hom., cov: 32)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

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.1252-10822T>C		intron	N/A	NP_001094896.1
	CRPPA	NM_001368197.1		c.1147-10822T>C		intron	N/A	NP_001355126.1
	CRPPA	NM_001101417.4		c.1102-10822T>C		intron	N/A	NP_001094887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.1252-10822T>C		intron	N/A	ENSP00000385478.2
	CRPPA	ENST00000399310.3	TSL:1	c.1102-10822T>C		intron	N/A	ENSP00000382249.3
	CRPPA	ENST00000676325.1		c.949-10822T>C		intron	N/A	ENSP00000502074.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119461 AN: 151680 Hom.: 48429 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.787 AC: 119532 AN: 151798 Hom.: 48457 Cov.: 32 AF XY: 0.792 AC XY: 58752 AN XY: 74174

African (AFR) AF: 0.577 AC: 23875 AN: 41382

American (AMR) AF: 0.884 AC: 13491 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3203 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4224 AN: 5142

South Asian (SAS) AF: 0.857 AC: 4117 AN: 4802

European-Finnish (FIN) AF: 0.885 AC: 9317 AN: 10532

Middle Eastern (MID) AF: 0.847 AC: 244 AN: 288

European-Non Finnish (NFE) AF: 0.863 AC: 58568 AN: 67902

Other (OTH) AF: 0.813 AC: 1716 AN: 2112

Alfa AF: 0.769 Hom.: 2782

Bravo AF: 0.779

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.24
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: rs7798339; hg19: chr7-16142246;