rs8111933

Positions:

• chr19-4795635-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FEM1A	NM_018708.3	c.*1771G>C		3_prime_UTR_variant	1/1	ENST00000269856.5	NP_061178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1A	ENST00000269856.5	c.*1771G>C		3_prime_UTR_variant	1/1	6	NM_018708.3	ENSP00000269856.3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99308 AN: 151148 Hom.: 32792 Cov.: 28

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.: 0 AF XY: 0.727 AC XY: 5031 AN XY: 6920

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.657 AC: 99404 AN: 151264 Hom.: 32829 Cov.: 28 AF XY: 0.658 AC XY: 48570 AN XY: 73850

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.646

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
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs8111933; hg19: chr19-4795647; COSMIC: COSV54163175; COSMIC: COSV54163175;