dbSNP rs8111933: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1A	NM_018708.3 link	c.*1771G>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000269856.5	NP_061178.1	Q9BSK4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FEM1A	ENST00000269856.5 link	c.*1771G>C	3_prime_UTR_variant	Exon 1 of 1	6	NM_018708.3	ENSP00000269856.3	Q9BSK4
ENSG00000269604	ENST00000596170.1 link	n.-76C>G	upstream_gene_variant		3
ENSG00000269604	ENST00000601192.1 link	n.-80C>G	upstream_gene_variant		4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over