rs509477

Positions:

• chr18-34979331-C-G
• chr18-34979331-C-T

Variant summary

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

The NM_001143827.3(MAPRE2):​c.24+790C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,958 control chromosomes in the GnomAD database, including 26,747 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 0.59 (26747 hom., cov: 32)
• Consequence: MAPRE2 NM_001143827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

Genes affected

MAPRE2 (HGNC:6891): (microtubule associated protein RP/EB family member 2) The protein encoded by this gene shares significant homology to the adenomatous polyposis coli (APC) protein-binding EB1 gene family. This protein is a microtubule-associated protein that is necessary for spindle symmetry during mitosis. It is thought to play a role in the tumorigenesis of colorectal cancers and the proliferative control of normal cells. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPRE2	NM_001143826.3	c.-70+2252C>G		intron_variant
MAPRE2	NM_001143827.3	c.24+790C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPRE2	ENST00000413393.5	c.-70+2252C>G		intron_variant		5		P4
MAPRE2	ENST00000436190.6	c.24+790C>G		intron_variant		2
MAPRE2	ENST00000587359.5	c.-326+2252C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88974 AN: 151840 Hom.: 26735 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.586 AC: 89004 AN: 151958 Hom.: 26747 Cov.: 32 AF XY: 0.583 AC XY: 43307 AN XY: 74246

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.623

Alfa AF: 0.616 Hom.: 3666

Bravo AF: 0.585

Asia WGS AF: 0.637 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs509477; hg19: chr18-32559295;