7-16091661-G-C

Position:

• chr7-16091661-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001101426.4(CRPPA):​c.*34C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,190,132 control chromosomes in the GnomAD database, including 1,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (172 hom., cov: 33)
  • Exomes 𝑓: 0.054 (1738 hom.)
• Consequence: CRPPA NM_001101426.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0900

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-16091661-G-C is Benign according to our data. Variant chr7-16091661-G-C is described in ClinVar as [Benign]. Clinvar id is 257460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-16091661-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.*34C>G		3_prime_UTR_variant	10/10	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001101417.4	c.*34C>G		3_prime_UTR_variant	9/9		NP_001094887.1
CRPPA	NM_001368197.1	c.*34C>G		3_prime_UTR_variant	9/9		NP_001355126.1
CRPPA	NR_160656.1	n.1455C>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.*34C>G		3_prime_UTR_variant	10/10	5	NM_001101426.4	ENSP00000385478	P1
CRPPA	ENST00000399310.3	c.*34C>G		3_prime_UTR_variant	9/9	1		ENSP00000382249
CRPPA	ENST00000675257.1	c.*34C>G		3_prime_UTR_variant	10/10			ENSP00000501664
CRPPA	ENST00000676325.1	c.*34C>G		3_prime_UTR_variant	11/11			ENSP00000502074

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6348 AN: 152054 Hom.: 172 Cov.: 33

Gnomad AFR AF: 0.00983

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0526

GnomAD3 exomes AF: 0.0434 AC: 6402 AN: 147588 Hom.: 188 AF XY: 0.0443 AC XY: 3446 AN XY: 77756

Gnomad AFR exome AF: 0.00874

Gnomad AMR exome AF: 0.0307

Gnomad ASJ exome AF: 0.0680

Gnomad EAS exome AF: 0.0000974

Gnomad SAS exome AF: 0.0328

Gnomad FIN exome AF: 0.0401

Gnomad NFE exome AF: 0.0604

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0535 AC: 55575 AN: 1037960 Hom.: 1738 Cov.: 13 AF XY: 0.0533 AC XY: 28093 AN XY: 527442

Gnomad4 AFR exome AF: 0.00847

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.0000888

Gnomad4 SAS exome AF: 0.0347

Gnomad4 FIN exome AF: 0.0401

Gnomad4 NFE exome AF: 0.0605

Gnomad4 OTH exome AF: 0.0523

GnomAD4 genome AF: 0.0417 AC: 6349 AN: 152172 Hom.: 172 Cov.: 33 AF XY: 0.0404 AC XY: 3006 AN XY: 74372

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0353

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0365 Hom.: 41

Bravo AF: 0.0411

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

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	-0.85
CADD	Benign	1.2
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16878689; hg19: chr7-16131286;