4-5880357-C-T

Variant names:

• chr4-5880357-C-T
• rs4292278
• NM_001014809.3:c.381+12232G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014809.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRMP1	NM_001014809.3	MANE Select	c.381+12232G>A		intron	N/A	NP_001014809.1
	CRMP1	NM_001313.5		c.39+7871G>A		intron	N/A	NP_001304.1
	CRMP1	NM_001288661.2		c.33+9268G>A		intron	N/A	NP_001275590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRMP1	ENST00000324989.12	TSL:1 MANE Select	c.381+12232G>A		intron	N/A	ENSP00000321606.7
	CRMP1	ENST00000397890.7	TSL:1	c.39+7871G>A		intron	N/A	ENSP00000380987.2
	CRMP1	ENST00000512574.1	TSL:2	c.33+9268G>A		intron	N/A	ENSP00000425742.1

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

African (AFR) AF: 0.311 AC: 12898 AN: 41448

American (AMR) AF: 0.0817 AC: 1251 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.00617 AC: 32 AN: 5188

South Asian (SAS) AF: 0.0850 AC: 410 AN: 4822

European-Finnish (FIN) AF: 0.0571 AC: 604 AN: 10586

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0497 AC: 3377 AN: 68000

Other (OTH) AF: 0.121 AC: 255 AN: 2116

Alfa AF: 0.0662 Hom.: 1153

Bravo AF: 0.137

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.54
PhyloP100		-1.5
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: rs4292278; hg19: chr4-5882084;