rs74997573

Variant names:

• chr4-1315477-C-T
• rs74997573
• NM_001017405.3:c.333C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-1315477-C-T
• chr4-1315477-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001017405.3(MAEA):​c.333C>T​(p.Ser111Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,613,876 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (134 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (119 hom.)
• Consequence: MAEA NM_001017405.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0730
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 4-1315477-C-T is Benign according to our data. Variant chr4-1315477-C-T is described in ClinVar as Benign. ClinVar VariationId is 787794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	NM_001017405.3	MANE Select	c.333C>T	p.Ser111Ser	synonymous	Exon 3 of 9	NP_001017405.1	Q7L5Y9-1
	MAEA	NM_001297432.2		c.330C>T	p.Ser110Ser	synonymous	Exon 3 of 9	NP_001284361.1	B4DVN3
	MAEA	NM_005882.5		c.333C>T	p.Ser111Ser	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.333C>T	p.Ser111Ser	synonymous	Exon 3 of 9	ENSP00000302830.4	Q7L5Y9-1
	MAEA	ENST00000503693.1	TSL:1	n.339C>T		non_coding_transcript_exon	Exon 3 of 5
	MAEA	ENST00000509531.5	TSL:1	n.333C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000426966.1	D6RDW4

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3314 AN: 152188 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00572 AC: 1435 AN: 250922 AF XY: 0.00410

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00235 AC: 3431 AN: 1461570 Hom.: 119 Cov.: 32 AF XY: 0.00209 AC XY: 1523 AN XY: 727098

African (AFR) AF: 0.0776 AC: 2599 AN: 33478

American (AMR) AF: 0.00532 AC: 238 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86256

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 53134

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000226 AC: 251 AN: 1111994

Other (OTH) AF: 0.00493 AC: 298 AN: 60392

GnomAD4 genome AF: 0.0218 AC: 3317 AN: 152306 Hom.: 134 Cov.: 32 AF XY: 0.0214 AC XY: 1595 AN XY: 74478

African (AFR) AF: 0.0751 AC: 3123 AN: 41562

American (AMR) AF: 0.00850 AC: 130 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68016

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00969 Hom.: 30

Bravo AF: 0.0250

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

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	-0.34
CADD	Benign	8.5
DANN	Benign	0.90
PhyloP100		0.073
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs74997573; hg19: chr4-1309265;