19-4794245-T-G

Variant names:

• chr19-4794245-T-G
• rs11085099
• NM_018708.3:c.*381T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 5 publications found

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]

ENSG00000269604 (HGNC:):

ACMG classification

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	Q9BSK4

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	Q9BSK4
	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.: 33

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.: 0 AF XY: 0.639 AC XY: 30877 AN XY: 48312

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

GnomAD4 genome AF: 0.663 AC: 100809 AN: 152122 Hom.: 33544 Cov.: 33 AF XY: 0.663 AC XY: 49281 AN XY: 74356

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

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
DANN	Benign	0.37
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11085099;

hg19: chr19-4794257;

COSMIC: COSV54164561;

COSMIC: COSV54164561;