rs604578

chr18-35089476-T-A

Variant summary

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

The NM_014268.4(MAPRE2):c.251-7970T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,966 control chromosomes in the GnomAD database, including 4,820 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 0.22 (4820 hom., cov: 32)
• Consequence: MAPRE2 NM_014268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPRE2	NM_014268.4	c.251-7970T>A		intron_variant		ENST00000300249.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPRE2	ENST00000300249.10	c.251-7970T>A		intron_variant		1	NM_014268.4	A1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32597 AN: 151848 Hom.: 4799 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.215 AC: 32675 AN: 151966 Hom.: 4820 Cov.: 32 AF XY: 0.216 AC XY: 16068 AN XY: 74286

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.183

Alfa AF: 0.171 Hom.: 391

Bravo AF: 0.223

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.0
Dann	Benign	0.68

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: rs604578; hg19: chr18-32669440;