18-35069531-A-T

Variant names:

• chr18-35069531-A-T
• rs659670
• NM_014268.4:c.123-664A>T

Variant summary

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

The NM_014268.4(MAPRE2):​c.123-664A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,994 control chromosomes in the GnomAD database, including 8,512 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 0.30 (8512 hom., cov: 32)
• Consequence: MAPRE2 NM_014268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPRE2	NM_014268.4	c.123-664A>T		intron_variant	Intron 1 of 6	ENST00000300249.10	NP_055083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPRE2	ENST00000300249.10	c.123-664A>T		intron_variant	Intron 1 of 6	1	NM_014268.4	ENSP00000300249.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45087 AN: 151874 Hom.: 8484 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.297 AC: 45176 AN: 151994 Hom.: 8512 Cov.: 32 AF XY: 0.298 AC XY: 22145 AN XY: 74302

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.269

Alfa AF: 0.237 Hom.: 669

Bravo AF: 0.316

Asia WGS AF: 0.403 AC: 1395 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.72

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: rs659670; hg19: chr18-32649495;