rs6057651

Positions:

• chr20-32822531-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000375571.6(MAPRE1):​c.-4+2503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,286 control chromosomes in the GnomAD database, including 32 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 (32 hom., cov: 33)
• Consequence: MAPRE1 ENST00000375571.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0183 (2782/152286) while in subpopulation SAS AF= 0.044 (212/4818). AF 95% confidence interval is 0.0392. There are 32 homozygotes in gnomad4. There are 1411 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2782 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE1	NM_012325.3	c.-4+2503G>A		intron_variant		ENST00000375571.6	NP_036457.1
MAPRE1	XM_011528696.3	c.-4+2614G>A		intron_variant			XP_011526998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPRE1	ENST00000375571.6	c.-4+2503G>A		intron_variant		1	NM_012325.3	ENSP00000364721	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2773 AN: 152168 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0183 AC: 2782 AN: 152286 Hom.: 32 Cov.: 33 AF XY: 0.0190 AC XY: 1411 AN XY: 74450

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0199 Hom.: 8

Bravo AF: 0.0165

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.76

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: rs6057651; hg19: chr20-31410337;