rs7782939

Variant names:

• chr7-16421268-T-G
• rs7782939
• NM_001101426.4:c.55A>C

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.55A>C​(p.Ser19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,297,340 control chromosomes in the GnomAD database, including 60,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6867 hom., cov: 33)
  • Exomes 𝑓: 0.30 (53827 hom.)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.69
• Publications: 16 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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

ENSG00000272537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036817193).
• BP6: Variant 7-16421268-T-G is Benign according to our data. Variant chr7-16421268-T-G is described in ClinVar as Benign. ClinVar VariationId is 129288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 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.55A>C	p.Ser19Arg	missense	Exon 1 of 10	NP_001094896.1	A4D126-1
	CRPPA	NM_001368197.1		c.55A>C	p.Ser19Arg	missense	Exon 1 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.55A>C	p.Ser19Arg	missense	Exon 1 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.55A>C	p.Ser19Arg	missense	Exon 1 of 10	ENSP00000385478.2	A4D126-1
	CRPPA	ENST00000399310.3	TSL:1	c.55A>C	p.Ser19Arg	missense	Exon 1 of 9	ENSP00000382249.3	A4D126-2
	CRPPA	ENST00000856526.1		c.55A>C	p.Ser19Arg	missense	Exon 1 of 8	ENSP00000526585.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45300 AN: 151428 Hom.: 6873 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.257 AC: 3585 AN: 13926 AF XY: 0.245

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.304 AC: 348776 AN: 1145802 Hom.: 53827 Cov.: 34 AF XY: 0.304 AC XY: 166475 AN XY: 548400

African (AFR) AF: 0.293 AC: 6839 AN: 23332

American (AMR) AF: 0.280 AC: 2757 AN: 9850

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 3759 AN: 15656

East Asian (EAS) AF: 0.269 AC: 7195 AN: 26774

South Asian (SAS) AF: 0.335 AC: 11335 AN: 33788

European-Finnish (FIN) AF: 0.292 AC: 11257 AN: 38486

Middle Eastern (MID) AF: 0.256 AC: 859 AN: 3358

European-Non Finnish (NFE) AF: 0.307 AC: 290780 AN: 948676

Other (OTH) AF: 0.305 AC: 13995 AN: 45882

GnomAD4 genome AF: 0.299 AC: 45311 AN: 151538 Hom.: 6867 Cov.: 33 AF XY: 0.300 AC XY: 22202 AN XY: 74058

African (AFR) AF: 0.294 AC: 12141 AN: 41296

American (AMR) AF: 0.288 AC: 4397 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1412 AN: 5036

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4812

European-Finnish (FIN) AF: 0.300 AC: 3160 AN: 10528

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20477 AN: 67814

Other (OTH) AF: 0.277 AC: 583 AN: 2104

Alfa AF: 0.291 Hom.: 806

Bravo AF: 0.296

TwinsUK AF: 0.317 AC: 1174

ALSPAC AF: 0.320 AC: 1232

ExAC AF: 0.119 AC: 1435

Asia WGS AF: 0.337 AC: 1170 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	1	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.4
DANN	Benign	0.79
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.14
Sift	Benign	0.88	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.24		Gain of methylation at S19 (P = 0.0183)
MPC		0.060
ClinPred		0.0010	T
GERP RS		-3.6
PromoterAI		0.12	Neutral
Varity_R		0.046
gMVP		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7782939; hg19: chr7-16460893; COSMIC: COSV67907237;