dbSNP rs1044386: FEM1A:c.*1413G>A (chr19-4795277-G-A) – 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.*1413G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 166,902 control chromosomes in the GnomAD database, including 3,408 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 0.19 ( 2963 hom., cov: 31)

Exomes 𝑓: 0.24 ( 445 hom. )

Consequence

FEM1A
NM_018708.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

8 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1A	NM_018708.3 link	c.*1413G>A		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.*1413G>A	3_prime_UTR_variant	Exon 1 of 1	6	NM_018708.3	ENSP00000269856.3	Q9BSK4
ENSG00000269604	ENST00000596170.1 link	n.283C>T	non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000269604	ENST00000601192.1 link	n.279C>T	non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28972

AN:

151814

Hom.:

2963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0459

Gnomad SAS

AF:

0.0568

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.238

AC:

3561

AN:

14978

Hom.:

445

Cov.:

AF XY:

0.236

AC XY:

1684

AN XY:

7130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.240

AC:

3525

AN:

14710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.154

AC:

AN:

156

Other (OTH)

AF:

0.130

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

151

303

454

606

757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.191

AC:

28994

AN:

151924

Hom.:

2963

Cov.:

AF XY:

0.189

AC XY:

14053

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.223

AC:

9249

AN:

41418

American (AMR)

AF:

0.142

AC:

2165

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

602

AN:

3470

East Asian (EAS)

AF:

0.0460

AC:

238

AN:

5174

South Asian (SAS)

AF:

0.0573

AC:

276

AN:

4816

European-Finnish (FIN)

AF:

0.232

AC:

2442

AN:

10520

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13469

AN:

67972

Other (OTH)

AF:

0.175

AC:

368

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1152

2304

3456

4608

5760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.422

Hom.:

7448

Bravo

AF:

0.184

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.56

(source)

DANN

Benign

0.49

PhyloP100

-1.9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over