Genetic Variant FEM1A:c.*381T>G (chr19-4794245-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018708.3(FEM1A):c.*381T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 244,732 control chromosomes in the GnomAD database, including 53,433 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 0.66 ( 33544 hom., cov: 33)

Exomes 𝑓: 0.64 ( 19889 hom. )

Consequence

FEM1A
NM_018708.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

5 publications found

Variant links:

Genes affected

FEM1A (HGNC:16934): (fem-1 homolog A) Enables EP4 subtype prostaglandin E2 receptor binding activity and ubiquitin ligase-substrate adaptor activity. Involved in negative regulation of inflammatory response and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Part of Cul2-RING ubiquitin ligase complex. Is active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

FEM1A links:

ENSG00000269604 (HGNC:):

ENSG00000269604 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018708.3. 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
	FEM1A	NM_018708.3	MANE Select	c.*381T>G		3_prime_UTR	Exon 1 of 1	NP_061178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1A	ENST00000269856.5	TSL:6 MANE Select	c.*381T>G		3_prime_UTR	Exon 1 of 1	ENSP00000269856.3
	ENSG00000269604	ENST00000601192.1	TSL:4	n.1311A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100720

AN:

152004

Hom.:

33512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.645

AC:

59689

AN:

92610

Hom.:

19889

Cov.:

AF XY:

0.639

AC XY:

30877

AN XY:

48312

show subpopulations

African (AFR)

AF:

0.680

AC:

1785

AN:

2626

American (AMR)

AF:

0.595

AC:

2459

AN:

4136

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

1142

AN:

1824

East Asian (EAS)

AF:

0.603

AC:

2429

AN:

4030

South Asian (SAS)

AF:

0.561

AC:

6613

AN:

11780

European-Finnish (FIN)

AF:

0.726

AC:

13013

AN:

17918

Middle Eastern (MID)

AF:

0.626

AC:

169

AN:

270

European-Non Finnish (NFE)

AF:

0.642

AC:

29416

AN:

45822

Other (OTH)

AF:

0.633

AC:

2663

AN:

4204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1002

2004

3007

4009

5011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.663

AC:

100809

AN:

152122

Hom.:

33544

Cov.:

AF XY:

0.663

AC XY:

49281

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.693

AC:

28763

AN:

41492

American (AMR)

AF:

0.613

AC:

9359

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2214

AN:

3470

East Asian (EAS)

AF:

0.627

AC:

3235

AN:

5162

South Asian (SAS)

AF:

0.580

AC:

2798

AN:

4828

European-Finnish (FIN)

AF:

0.734

AC:

7769

AN:

10586

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.655

AC:

44540

AN:

67986

Other (OTH)

AF:

0.653

AC:

1382

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1786

3572

5359

7145

8931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.655

Hom.:

11825

Bravo

AF:

0.651

Asia WGS

AF:

0.641

AC:

2231

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.0

(source)

DANN

Benign

0.37

PhyloP100

0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over