3-184711345-ATCCTCCTCCTCC-ATCCTCCTCCTCCTCCTCC

Variant names:

• chr3-184711345-A-ATCCTCC
• rs34995413
• NM_022149.5:c.471_476dupGGAGGA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_022149.5(MAGEF1):​c.471_476dupGGAGGA​(p.Glu157_Glu158dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,567,536 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (24 hom.)
• Consequence: MAGEF1 NM_022149.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156
• Publications: 12 publications found

Genes affected

MAGEF1 (HGNC:29639): (MAGE family member F1) This intronless gene encodes a member of the MAGE superfamily. It is ubiquitously expressed in normal tissues and in tumor cells. This gene includes a microsatellite repeat in the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_022149.5
• BP6: Variant 3-184711345-A-ATCCTCC is Benign according to our data. Variant chr3-184711345-A-ATCCTCC is described in ClinVar as Benign. ClinVar VariationId is 403067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00855 (1287/150552) while in subpopulation AFR AF = 0.0277 (1135/40980). AF 95% confidence interval is 0.0264. There are 12 homozygotes in GnomAd4. There are 609 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEF1	NM_022149.5	c.471_476dupGGAGGA	p.Glu157_Glu158dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000317897.5	NP_071432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEF1	ENST00000317897.5	c.471_476dupGGAGGA	p.Glu157_Glu158dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_022149.5	ENSP00000315064.3

Frequencies

GnomAD3 genomes AF: 0.00853 AC: 1283 AN: 150432 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00284

Gnomad ASJ AF: 0.00984

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000632

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000800

Gnomad OTH AF: 0.00674

GnomAD2 exomes AF: 0.00301 AC: 730 AN: 242436 AF XY: 0.00243

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00152

Gnomad ASJ exome AF: 0.0117

Gnomad EAS exome AF: 0.000441

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000603

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.00159 AC: 2257 AN: 1416984 Hom.: 24 Cov.: 88 AF XY: 0.00147 AC XY: 1035 AN XY: 705666

African (AFR) AF: 0.0332 AC: 1097 AN: 33008

American (AMR) AF: 0.00180 AC: 80 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 311 AN: 25602

East Asian (EAS) AF: 0.000253 AC: 10 AN: 39552

South Asian (SAS) AF: 0.000248 AC: 21 AN: 84684

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 50980

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5684

European-Non Finnish (NFE) AF: 0.000510 AC: 548 AN: 1074198

Other (OTH) AF: 0.00297 AC: 175 AN: 58952

GnomAD4 genome AF: 0.00855 AC: 1287 AN: 150552 Hom.: 12 Cov.: 0 AF XY: 0.00828 AC XY: 609 AN XY: 73526

African (AFR) AF: 0.0277 AC: 1135 AN: 40980

American (AMR) AF: 0.00284 AC: 43 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00984 AC: 34 AN: 3454

East Asian (EAS) AF: 0.000392 AC: 2 AN: 5096

South Asian (SAS) AF: 0.000633 AC: 3 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.000800 AC: 54 AN: 67476

Other (OTH) AF: 0.00715 AC: 15 AN: 2098

Alfa AF: 0.00323 Hom.: 3040

EpiCase AF: 0.000709

EpiControl AF: 0.000949

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=82/18	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34995413; hg19: chr3-184429133;