chr7-16308637-A-AAAC

Position:

• chr7-16308637-A-AAAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001101426.4(CRPPA):​c.685-11_685-10insGTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,406,232 control chromosomes in the GnomAD database, including 1,186 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (237 hom., cov: 32)
  • Exomes 𝑓: 0.024 (949 hom.)
• Consequence: CRPPA NM_001101426.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.808

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 -16 ACMG points.

• BP6: Variant 7-16308637-A-AAAC is Benign according to our data. Variant chr7-16308637-A-AAAC is described in ClinVar as [Likely_benign]. Clinvar id is 226676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.685-11_685-10insGTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000407010.7	NP_001094896.1
CRPPA	NM_001101417.4	c.535-11_535-10insGTT		splice_polypyrimidine_tract_variant, intron_variant			NP_001094887.1
CRPPA	NM_001368197.1	c.685-7172_685-7171insGTT		intron_variant			NP_001355126.1
CRPPA	NR_160656.1	n.901-30412_901-30411insGTT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.685-11_685-10insGTT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001101426.4	ENSP00000385478	P1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6820 AN: 152162 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0423 AC: 9287 AN: 219382 Hom.: 318 AF XY: 0.0395 AC XY: 4659 AN XY: 118030

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.0678

Gnomad ASJ exome AF: 0.0519

Gnomad EAS exome AF: 0.157

Gnomad SAS exome AF: 0.0349

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0241 AC: 30186 AN: 1253954 Hom.: 949 Cov.: 18 AF XY: 0.0244 AC XY: 15420 AN XY: 633132

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.0660

Gnomad4 ASJ exome AF: 0.0515

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.0329

Gnomad4 FIN exome AF: 0.0249

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0318

GnomAD4 genome AF: 0.0449 AC: 6836 AN: 152278 Hom.: 237 Cov.: 32 AF XY: 0.0462 AC XY: 3443 AN XY: 74448

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0412

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0582

Bravo AF: 0.0507

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 09, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 25, 2015	c.685-13_685-11dup in intron 3 of ISPD: This variant is not expected to have cli nical significance because it has been identified in 17.2% (896/5208) of East As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs142647500). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 10, 2014	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 08, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 18, 2019	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital Muscular Dystrophy, alpha-dystroglycan related Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142647500; hg19: chr7-16348262;