7-16091661-G-C

Variant names:

• chr7-16091661-G-C
• rs16878689
• NM_001101426.4:c.*34C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• myopathy caused by variation in CRPPA

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2U

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 257460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	NM_001101426.4	MANE Select	c.*34C>G		3_prime_UTR	Exon 10 of 10	NP_001094896.1	A4D126-1
	CRPPA	NM_001368197.1		c.*34C>G		3_prime_UTR	Exon 9 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.*34C>G		3_prime_UTR	Exon 9 of 9	NP_001094887.1	A0A140VJM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.*34C>G		3_prime_UTR	Exon 10 of 10	ENSP00000385478.2	A4D126-1
	CRPPA	ENST00000399310.3	TSL:1	c.*34C>G		3_prime_UTR	Exon 9 of 9	ENSP00000382249.3	A4D126-2
	CRPPA	ENST00000856526.1		c.*34C>G		3_prime_UTR	Exon 8 of 8	ENSP00000526585.1

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

GnomAD2 exomes AF: 0.0434 AC: 6402 AN: 147588 AF XY: 0.0443

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 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

African (AFR) AF: 0.00847 AC: 203 AN: 23964

American (AMR) AF: 0.0331 AC: 1086 AN: 32844

Ashkenazi Jewish (ASJ) AF: 0.0684 AC: 1559 AN: 22794

East Asian (EAS) AF: 0.0000888 AC: 3 AN: 33800

South Asian (SAS) AF: 0.0347 AC: 2400 AN: 69198

European-Finnish (FIN) AF: 0.0401 AC: 1957 AN: 48782

Middle Eastern (MID) AF: 0.0570 AC: 283 AN: 4968

European-Non Finnish (NFE) AF: 0.0605 AC: 45666 AN: 755410

Other (OTH) AF: 0.0523 AC: 2418 AN: 46200

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

African (AFR) AF: 0.00982 AC: 408 AN: 41534

American (AMR) AF: 0.0469 AC: 716 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0353 AC: 170 AN: 4822

European-Finnish (FIN) AF: 0.0436 AC: 461 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0613 AC: 4170 AN: 67988

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0365 Hom.: 41

Bravo AF: 0.0411

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16878689; hg19: chr7-16131286;