4-5880357-C-T

Position:

• chr4-5880357-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001014809.3(CRMP1):​c.381+12232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,142 control chromosomes in the GnomAD database, including 2,245 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (2245 hom., cov: 33)
• Consequence: CRMP1 NM_001014809.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRMP1	NM_001014809.3	c.381+12232G>A		intron_variant		ENST00000324989.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRMP1	ENST00000324989.12	c.381+12232G>A		intron_variant		1	NM_001014809.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19230 AN: 152024 Hom.: 2239 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19267 AN: 152142 Hom.: 2245 Cov.: 33 AF XY: 0.125 AC XY: 9295 AN XY: 74376

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.00617

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0497

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0593 Hom.: 589

Bravo AF: 0.137

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.54

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: rs4292278; hg19: chr4-5882084;