rs6057651

Variant names:

• chr20-32822531-G-A
• rs6057651
• NM_012325.3:c.-4+2503G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012325.3(MAPRE1):​c.-4+2503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,286 control chromosomes in the GnomAD database, including 32 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 0.018 (32 hom., cov: 33)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 9 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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0183 (2782/152286) while in subpopulation SAS AF = 0.044 (212/4818). AF 95% confidence interval is 0.0392. There are 32 homozygotes in GnomAd4. There are 1411 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2782 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	NM_012325.3	MANE Select	c.-4+2503G>A		intron	N/A	NP_036457.1	Q15691

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	ENST00000375571.6	TSL:1 MANE Select	c.-4+2503G>A		intron	N/A	ENSP00000364721.5	Q15691
	MAPRE1	ENST00000912292.1		c.-2078G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000582351.1
	MAPRE1	ENST00000912296.1		c.-2034G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000582355.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2773 AN: 152168 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0183 AC: 2782 AN: 152286 Hom.: 32 Cov.: 33 AF XY: 0.0190 AC XY: 1411 AN XY: 74450

African (AFR) AF: 0.0205 AC: 853 AN: 41566

American (AMR) AF: 0.0103 AC: 158 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5184

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4818

European-Finnish (FIN) AF: 0.0166 AC: 176 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0191 AC: 1302 AN: 68034

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.0189 Hom.: 16

Bravo AF: 0.0165

Asia WGS AF: 0.0410 AC: 141 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	4.6
DANN	Benign	0.76
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6057651;

hg19: chr20-31410337;