chr4-1315453-C-T

Variant names:

• chr4-1315453-C-T
• rs141399202
• NM_001017405.3:c.309C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001017405.3(MAEA):​c.309C>T​(p.Ile103Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MAEA NM_001017405.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.193
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-1315453-C-T is Benign according to our data. Variant chr4-1315453-C-T is described in ClinVar as Benign. ClinVar VariationId is 717838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.193 with no splicing effect.
• BS2: High AC in GnomAd4 at 199 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	NM_001017405.3	MANE Select	c.309C>T	p.Ile103Ile	synonymous	Exon 3 of 9	NP_001017405.1	Q7L5Y9-1
	MAEA	NM_001297432.2		c.306C>T	p.Ile102Ile	synonymous	Exon 3 of 9	NP_001284361.1	B4DVN3
	MAEA	NM_005882.5		c.309C>T	p.Ile103Ile	synonymous	Exon 3 of 8	NP_005873.2	Q7L5Y9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	ENST00000303400.9	TSL:1 MANE Select	c.309C>T	p.Ile103Ile	synonymous	Exon 3 of 9	ENSP00000302830.4	Q7L5Y9-1
	MAEA	ENST00000503693.1	TSL:1	n.315C>T		non_coding_transcript_exon	Exon 3 of 5
	MAEA	ENST00000509531.5	TSL:1	n.309C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000426966.1	D6RDW4

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000307 AC: 77 AN: 250902 AF XY: 0.000250

Gnomad AFR exome AF: 0.00432

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 167 AN: 1461564 Hom.: 0 Cov.: 32 AF XY: 0.0000880 AC XY: 64 AN XY: 727098

African (AFR) AF: 0.00412 AC: 138 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111998

Other (OTH) AF: 0.000132 AC: 8 AN: 60390

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74468

African (AFR) AF: 0.00457 AC: 190 AN: 41586

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000919 Hom.: 1

Bravo AF: 0.00143

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.92
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

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: rs141399202; hg19: chr4-1309241; COSMIC: COSV53264232; COSMIC: COSV53264232;