2-27025376-C-T

Variant names:

• chr2-27025376-C-T
• rs2289408
• NM_012326.4:c.470-207C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_012326.4(MAPRE3):​c.470-207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 152,352 control chromosomes in the GnomAD database, including 6 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 0.0014 (6 hom., cov: 33)
• Consequence: MAPRE3 NM_012326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 1 publications found

Genes affected

MAPRE3 (HGNC:6892): (microtubule associated protein RP/EB family member 3) The protein encoded by this gene is a member of the RP/EB family of genes. The protein localizes to the cytoplasmic microtubule network and binds APCL, a homolog of the adenomatous polyposis coli tumor suppressor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0014 (213/152352) while in subpopulation EAS AF = 0.0388 (201/5174). AF 95% confidence interval is 0.0345. There are 6 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPRE3	NM_012326.4	c.470-207C>T		intron_variant	Intron 4 of 6	ENST00000233121.7	NP_036458.2
MAPRE3	NM_001303050.2	c.470-207C>T		intron_variant	Intron 4 of 6		NP_001289979.1
MAPRE3	NM_001410716.1	c.425-207C>T		intron_variant	Intron 4 of 6		NP_001397645.1
MAPRE3	XM_047443728.1	c.470-207C>T		intron_variant	Intron 4 of 6		XP_047299684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPRE3	ENST00000233121.7	c.470-207C>T		intron_variant	Intron 4 of 6	1	NM_012326.4	ENSP00000233121.2

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152234 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0388

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152352 Hom.: 6 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.000392 AC: 6 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0388 AC: 201 AN: 5174

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00190 Hom.: 3

Bravo AF: 0.00148

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.50
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2289408; hg19: chr2-27248244;