7-16088220-G-A

Position:

• chr7-16088220-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001101426.4(CRPPA):​c.*3475C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,136 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.619

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-16088220-G-A is Benign according to our data. Variant chr7-16088220-G-A is described in ClinVar as [Benign]. Clinvar id is 359491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2328/152136) while in subpopulation NFE AF= 0.0253 (1721/68004). AF 95% confidence interval is 0.0243. There are 29 homozygotes in gnomad4. There are 1063 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.*3475C>T		3_prime_UTR_variant	10/10	ENST00000407010.7
CRPPA	NM_001101417.4	c.*3475C>T		3_prime_UTR_variant	9/9
CRPPA	NM_001368197.1	c.*3475C>T		3_prime_UTR_variant	9/9
CRPPA	NR_160656.1	n.4896C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.*3475C>T		3_prime_UTR_variant	10/10	5	NM_001101426.4	P1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2331 AN: 152018 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00377

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00996

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0177

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0153 AC: 2328 AN: 152136 Hom.: 29 Cov.: 32 AF XY: 0.0143 AC XY: 1063 AN XY: 74374

Gnomad4 AFR AF: 0.00373

Gnomad4 AMR AF: 0.00995

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0113

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00381 Hom.: 2

Bravo AF: 0.0153

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital Muscular Dystrophy, alpha-dystroglycan related Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs80341455; hg19: chr7-16127845;