4-1297325-G-T

Variant names:

• chr4-1297325-G-T
• rs13108904
• NM_001017405.3:c.69+7343G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017405.3(MAEA):​c.69+7343G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,174 control chromosomes in the GnomAD database, including 12,011 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 0.36 (12011 hom., cov: 33)
• Consequence: MAEA NM_001017405.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 14 publications found

Genes affected

MAEA (HGNC:13731): (macrophage erythroblast attacher, E3 ubiquitin ligase) This gene encodes a protein that mediates the attachment of erythroblasts to macrophages. This attachment promotes terminal maturation and enucleation of erythroblasts, presumably by suppressing apoptosis. The encoded protein is an integral membrane protein with the N-terminus on the extracellular side and the C-terminus on the cytoplasmic side of the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017405.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	NM_001017405.3	MANE Select	c.69+7343G>T		intron	N/A	NP_001017405.1
	MAEA	NM_005882.5		c.69+7343G>T		intron	N/A	NP_005873.2
	MAEA	NM_001297430.2		c.69+7343G>T		intron	N/A	NP_001284359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	ENST00000303400.9	TSL:1 MANE Select	c.69+7343G>T		intron	N/A	ENSP00000302830.4
	MAEA	ENST00000503693.1	TSL:1	n.75+7343G>T		intron	N/A
	MAEA	ENST00000509531.5	TSL:1	n.69+7343G>T		intron	N/A	ENSP00000426966.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55220 AN: 152056 Hom.: 12009 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.363 AC: 55223 AN: 152174 Hom.: 12011 Cov.: 33 AF XY: 0.361 AC XY: 26856 AN XY: 74404

African (AFR) AF: 0.135 AC: 5610 AN: 41518

American (AMR) AF: 0.347 AC: 5311 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1511 AN: 3470

East Asian (EAS) AF: 0.0931 AC: 482 AN: 5180

South Asian (SAS) AF: 0.360 AC: 1737 AN: 4828

European-Finnish (FIN) AF: 0.537 AC: 5691 AN: 10590

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33600 AN: 67966

Other (OTH) AF: 0.338 AC: 714 AN: 2114

Alfa AF: 0.434 Hom.: 5454

Bravo AF: 0.335

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.48
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13108904; hg19: chr4-1291113;