rs242553

Positions:

• chr20-32824019-T-C
• chr20-32824019-T-G

Variant summary

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

The NM_012325.3(MAPRE1):​c.-3-1906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,208 control chromosomes in the GnomAD database, including 38,204 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 0.69 (38204 hom., cov: 33)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE1	NM_012325.3	c.-3-1906T>C		intron_variant		ENST00000375571.6	NP_036457.1
MAPRE1	XM_011528696.3	c.-3-1906T>C		intron_variant			XP_011526998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPRE1	ENST00000375571.6	c.-3-1906T>C		intron_variant		1	NM_012325.3	ENSP00000364721.5

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104640 AN: 152088 Hom.: 38134 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.688 AC: 104770 AN: 152208 Hom.: 38204 Cov.: 33 AF XY: 0.688 AC XY: 51225 AN XY: 74402

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.626

Alfa AF: 0.627 Hom.: 3878

Bravo AF: 0.708

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.45

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: rs242553; hg19: chr20-31411825;