7-16215977-A-T

Variant names:

• chr7-16215977-A-T
• rs4389828
• NM_001101426.4:c.1251+89T>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001101426.4(CRPPA):​c.1251+89T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,037,554 control chromosomes in the GnomAD database, including 224,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31397 hom., cov: 32)
  • Exomes 𝑓: 0.66 (192621 hom.)
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.501

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-AS1 (HGNC:48962): (CRPPA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-16215977-A-T is Benign according to our data. Variant chr7-16215977-A-T is described in ClinVar as [Benign]. Clinvar id is 682001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.1251+89T>A		intron_variant	Intron 9 of 9	ENST00000407010.7	NP_001094896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.1251+89T>A		intron_variant	Intron 9 of 9	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97265 AN: 151942 Hom.: 31358 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.657 AC: 581967 AN: 885494 Hom.: 192621 AF XY: 0.657 AC XY: 295872 AN XY: 450526

Gnomad4 AFR exome AF: 0.546

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.641

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.640 AC: 97355 AN: 152060 Hom.: 31397 Cov.: 32 AF XY: 0.645 AC XY: 47965 AN XY: 74338

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.628

Alfa AF: 0.564 Hom.: 1690

Bravo AF: 0.630

Asia WGS AF: 0.617 AC: 2134 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.69

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: rs4389828; hg19: chr7-16255602; COSMIC: COSV67909715;