rs11247991

Variant names:

• chr4-1314776-A-G
• rs11247991
• NM_001017405.3:c.253-621A>G

Variant summary

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

The NM_001017405.3(MAEA):​c.253-621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 152,316 control chromosomes in the GnomAD database, including 1,372 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 0.094 (1372 hom., cov: 33)
• Consequence: MAEA NM_001017405.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAEA	NM_001017405.3	c.253-621A>G		intron_variant	Intron 2 of 8	ENST00000303400.9	NP_001017405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAEA	ENST00000303400.9	c.253-621A>G		intron_variant	Intron 2 of 8	1	NM_001017405.3	ENSP00000302830.4

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14273 AN: 152198 Hom.: 1368 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0940 AC: 14315 AN: 152316 Hom.: 1372 Cov.: 33 AF XY: 0.0993 AC XY: 7399 AN XY: 74482

African (AFR) AF: 0.132 AC: 5488 AN: 41570

American (AMR) AF: 0.215 AC: 3290 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2164 AN: 5172

South Asian (SAS) AF: 0.154 AC: 742 AN: 4828

European-Finnish (FIN) AF: 0.0465 AC: 494 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1733 AN: 68026

Other (OTH) AF: 0.0761 AC: 161 AN: 2116

Alfa AF: 0.0822 Hom.: 195

Bravo AF: 0.111

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs11247991; hg19: chr4-1308564;