chr20-32832003-A-C

Variant names:

• chr20-32832003-A-C
• rs6057652
• NM_012325.3:c.122-1714A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012325.3(MAPRE1):​c.122-1714A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 151,526 control chromosomes in the GnomAD database, including 28 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 0.018 (28 hom., cov: 32)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 7 publications found

Genes affected

MAPRE1 (HGNC:6890): (microtubule associated protein RP/EB family member 1) The protein encoded by this gene was first identified by its binding to the APC protein which is often mutated in familial and sporadic forms of colorectal cancer. This protein localizes to microtubules, especially the growing ends, in interphase cells. During mitosis, the protein is associated with the centrosomes and spindle microtubules. The protein also associates with components of the dynactin complex and the intermediate chain of cytoplasmic dynein. Because of these associations, it is thought that this protein is involved in the regulation of microtubule structures and chromosome stability. This gene is a member of the RP/EB family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0181 (2744/151526) while in subpopulation SAS AF = 0.0436 (209/4790). AF 95% confidence interval is 0.0388. There are 28 homozygotes in GnomAd4. There are 1388 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2744 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012325.3. 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
	MAPRE1	NM_012325.3	MANE Select	c.122-1714A>C		intron	N/A	NP_036457.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	ENST00000375571.6	TSL:1 MANE Select	c.122-1714A>C		intron	N/A	ENSP00000364721.5
	MAPRE1	ENST00000908452.1		c.122-1714A>C		intron	N/A	ENSP00000578511.1
	MAPRE1	ENST00000908453.1		c.122-1714A>C		intron	N/A	ENSP00000578512.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2735 AN: 151452 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0181 AC: 2744 AN: 151526 Hom.: 28 Cov.: 32 AF XY: 0.0188 AC XY: 1388 AN XY: 73978

African (AFR) AF: 0.0203 AC: 838 AN: 41334

American (AMR) AF: 0.0102 AC: 155 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5164

South Asian (SAS) AF: 0.0436 AC: 209 AN: 4790

European-Finnish (FIN) AF: 0.0162 AC: 167 AN: 10318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0191 AC: 1295 AN: 67934

Other (OTH) AF: 0.0124 AC: 26 AN: 2100

Alfa AF: 0.0184 Hom.: 15

Bravo AF: 0.0165

Asia WGS AF: 0.0410 AC: 141 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.56
PhyloP100		0.66
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: rs6057652; hg19: chr20-31419809;