4-1297325-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAEA	NM_001017405.3	c.69+7343G>T		intron_variant	Intron 1 of 8	ENST00000303400.9	NP_001017405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAEA	ENST00000303400.9	c.69+7343G>T		intron_variant	Intron 1 of 8	1	NM_001017405.3	ENSP00000302830.4

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.0931

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.338

Alfa AF: 0.442 Hom.: 4417

Bravo AF: 0.335

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs13108904; hg19: chr4-1291113;