rs509477

Variant names:

• chr18-34979331-C-G
• rs509477
• NM_001143827.3:c.24+790C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

MAPRE2 Gene-Disease associations (from GenCC):

• skin creases, congenital symmetric circumferential, 2

  Inheritance: Unknown, AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• multiple benign circumferential skin creases on limbs

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143827.3. 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
	MAPRE2	NM_001143827.3		c.24+790C>G		intron	N/A	NP_001137299.1	Q15555-3
	MAPRE2	NM_001143826.3		c.-70+2252C>G		intron	N/A	NP_001137298.1	Q15555-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	ENST00000436190.6	TSL:2	c.24+790C>G		intron	N/A	ENSP00000407723.1	Q15555-3
	MAPRE2	ENST00000413393.5	TSL:5	c.-70+2252C>G		intron	N/A	ENSP00000396074.1	Q15555-5
	MAPRE2	ENST00000591734.5	TSL:2	c.-70+2252C>G		intron	N/A	ENSP00000468216.1	K7ERD8

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

African (AFR) AF: 0.441 AC: 18266 AN: 41438

American (AMR) AF: 0.635 AC: 9696 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2154 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3621 AN: 5170

South Asian (SAS) AF: 0.620 AC: 2986 AN: 4818

European-Finnish (FIN) AF: 0.553 AC: 5832 AN: 10540

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44465 AN: 67938

Other (OTH) AF: 0.623 AC: 1314 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs509477; hg19: chr18-32559295;