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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1A	NM_018708.3 link	c.*381T>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000269856.5	NP_061178.1	Q9BSK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1A	ENST00000269856.5 link	c.*381T>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_018708.3	ENSP00000269856.3		Q9BSK4
ENSG00000269604	ENST00000601192.1 link	n.1311A>C		non_coding_transcript_exon_variant	Exon 1 of 2	4

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

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

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 v4.3

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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19-4794245-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over