NM_012325.3:c.476-199C>T

Variant names:

• chr20-32839536-C-T
• rs2235760
• NM_012325.3:c.476-199C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012325.3(MAPRE1):​c.476-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,080 control chromosomes in the GnomAD database, including 5,086 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 0.24 (5086 hom., cov: 32)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 13 publications found

Genes affected

MAPRE1 (HGNC:6890): (microtubule associated protein RP/EB family member 1) The protein encoded by this gene was first identified by its binding to the APC protein which is often mutated in familial and sporadic forms of colorectal cancer. This protein localizes to microtubules, especially the growing ends, in interphase cells. During mitosis, the protein is associated with the centrosomes and spindle microtubules. The protein also associates with components of the dynactin complex and the intermediate chain of cytoplasmic dynein. Because of these associations, it is thought that this protein is involved in the regulation of microtubule structures and chromosome stability. This gene is a member of the RP/EB family. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012325.3. 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
	MAPRE1	NM_012325.3	MANE Select	c.476-199C>T		intron	N/A	NP_036457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	ENST00000375571.6	TSL:1 MANE Select	c.476-199C>T		intron	N/A	ENSP00000364721.5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36375 AN: 151962 Hom.: 5073 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.239 AC: 36421 AN: 152080 Hom.: 5086 Cov.: 32 AF XY: 0.242 AC XY: 17989 AN XY: 74350

African (AFR) AF: 0.382 AC: 15834 AN: 41452

American (AMR) AF: 0.217 AC: 3320 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1827 AN: 5162

South Asian (SAS) AF: 0.299 AC: 1440 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10594

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10906 AN: 67988

Other (OTH) AF: 0.215 AC: 455 AN: 2114

Alfa AF: 0.209 Hom.: 677

Bravo AF: 0.252

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.78
PhyloP100		-0.078
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: rs2235760; hg19: chr20-31427342; COSMIC: COSV65032934; COSMIC: COSV65032934;