7-16460517-A-G

Position:

• chr7-16460517-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007060223.1(LOC105375168):​n.580+8686A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,114 control chromosomes in the GnomAD database, including 65,762 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 0.93 (65762 hom., cov: 31)
• Consequence: LOC105375168 XR_007060223.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

LOC105375168 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105375168	XR_007060223.1	n.580+8686A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000674759.1	c.-47+35863T>C		intron_variant				ENSP00000502749
CRPPA	ENST00000675257.1	c.-47+35863T>C		intron_variant				ENSP00000501664

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141249 AN: 151996 Hom.: 65710 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.929 AC: 141361 AN: 152114 Hom.: 65762 Cov.: 31 AF XY: 0.932 AC XY: 69268 AN XY: 74360

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.918

Alfa AF: 0.913 Hom.: 123276

Bravo AF: 0.930

Asia WGS AF: 0.932 AC: 3240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10270805; hg19: chr7-16500142;