rs2235760

Positions:

• chr20-32839536-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE1	NM_012325.3	c.476-199C>T		intron_variant		ENST00000375571.6	NP_036457.1
MAPRE1	XM_011528696.3	c.476-199C>T		intron_variant			XP_011526998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPRE1	ENST00000375571.6	c.476-199C>T		intron_variant		1	NM_012325.3	ENSP00000364721	P1

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

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.215

Alfa AF: 0.204 Hom.: 619

Bravo AF: 0.252

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.78

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: rs2235760; hg19: chr20-31427342; COSMIC: COSV65032934; COSMIC: COSV65032934;