Genetic Variant FEM1A:c.*1771G>C (chr19-4795635-G-C) – 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.*1771G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 165,824 control chromosomes in the GnomAD database, including 36,625 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 ( 32829 hom., cov: 28)

Exomes 𝑓: 0.72 ( 3796 hom. )

Consequence

FEM1A
NM_018708.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.05

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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 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.*1771G>C		3_prime_UTR	Exon 1 of 1	NP_061178.1	Q9BSK4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FEM1A	ENST00000269856.5	TSL:6 MANE Select	c.*1771G>C	3_prime_UTR	Exon 1 of 1	ENSP00000269856.3	Q9BSK4
ENSG00000269604	ENST00000596170.1	TSL:3	n.-76C>G	upstream_gene	N/A
ENSG00000269604	ENST00000601192.1	TSL:4	n.-80C>G	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99308

AN:

151148

Hom.:

32792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.609

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.638

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.642

GnomAD4 exome

AF:

0.722

AC:

10514

AN:

14560

Hom.:

3796

Cov.:

AF XY:

0.727

AC XY:

5031

AN XY:

6920

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.723

AC:

10335

AN:

14296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.730

AC:

108

AN:

148

Other (OTH)

AF:

0.628

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

133

267

400

534

667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.657

AC:

99404

AN:

151264

Hom.:

32829

Cov.:

AF XY:

0.658

AC XY:

48570

AN XY:

73850

show subpopulations

African (AFR)

AF:

0.699

AC:

28736

AN:

41134

American (AMR)

AF:

0.609

AC:

9246

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

2183

AN:

3468

East Asian (EAS)

AF:

0.624

AC:

3216

AN:

5154

South Asian (SAS)

AF:

0.572

AC:

2747

AN:

4804

European-Finnish (FIN)

AF:

0.724

AC:

7520

AN:

10388

Middle Eastern (MID)

AF:

0.662

AC:

192

AN:

290

European-Non Finnish (NFE)

AF:

0.644

AC:

43653

AN:

67836

Other (OTH)

AF:

0.646

AC:

1361

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1680

3359

5039

6718

8398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.654

Hom.:

4012

Bravo

AF:

0.646

Asia WGS

AF:

0.635

AC:

2210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.45

(source)

DANN

Benign

0.38

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism

(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