rs6579038

Positions:

• chr20-32842964-A-G

Variant summary

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

The NM_012325.3(MAPRE1):​c.597+3108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 152,120 control chromosomes in the GnomAD database, including 281 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 0.060 (281 hom., cov: 32)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE1	NM_012325.3	c.597+3108A>G		intron_variant		ENST00000375571.6	NP_036457.1
MAPRE1	XM_011528696.3	c.597+3108A>G		intron_variant			XP_011526998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPRE1	ENST00000375571.6	c.597+3108A>G		intron_variant		1	NM_012325.3	ENSP00000364721.5

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9147 AN: 152002 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0604 AC: 9182 AN: 152120 Hom.: 281 Cov.: 32 AF XY: 0.0596 AC XY: 4436 AN XY: 74370

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0848

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.0403

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0570 Hom.: 372

Bravo AF: 0.0600

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.44

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: rs6579038; hg19: chr20-31430770;