rs11247991

chr4-1314776-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAEA	NM_001017405.3	c.253-621A>G		intron_variant		ENST00000303400.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAEA	ENST00000303400.9	c.253-621A>G		intron_variant		1	NM_001017405.3	P1

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0761

Alfa AF: 0.0809 Hom.: 188

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

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: rs11247991; hg19: chr4-1308564;