chr7-16441663-C-T

Variant names:

• chr7-16441663-C-T
• rs1921832
• ENST00000675257.1:c.-46-35326G>A

Variant summary

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

The ENST00000675257.1(CRPPA):​c.-46-35326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 152,070 control chromosomes in the GnomAD database, including 70 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 0.026 (70 hom., cov: 32)
• Consequence: CRPPA ENST00000675257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 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.-46-35326G>A		intron	N/A	ENSP00000501664.1	A0A6Q8PF75
	CRPPA	ENST00000674759.1		c.-46-35326G>A		intron	N/A	ENSP00000502749.1	A0A6Q8PHI3
	ENSG00000272537	ENST00000605985.2	TSL:6	n.394+7276C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3956 AN: 151952 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0259

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

GnomAD4 genome AF: 0.0260 AC: 3958 AN: 152070 Hom.: 70 Cov.: 32 AF XY: 0.0272 AC XY: 2024 AN XY: 74338

African (AFR) AF: 0.0364 AC: 1512 AN: 41494

American (AMR) AF: 0.0142 AC: 216 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.116 AC: 604 AN: 5186

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4818

European-Finnish (FIN) AF: 0.0270 AC: 285 AN: 10558

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1083 AN: 67976

Other (OTH) AF: 0.0270 AC: 57 AN: 2108

Alfa AF: 0.0195 Hom.: 24

Bravo AF: 0.0262

Asia WGS AF: 0.0830 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1921832; hg19: chr7-16481288;