rs1044386

Positions:

• chr19-4795277-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FEM1A	NM_018708.3	c.*1413G>A		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.*1413G>A		3_prime_UTR_variant	1/1	6	NM_018708.3	ENSP00000269856.3
ENSG00000269604	ENST00000596170.1	n.283C>T		non_coding_transcript_exon_variant	1/2	3
ENSG00000269604	ENST00000601192.1	n.279C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28972 AN: 151814 Hom.: 2963 Cov.: 31

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.: 0 AF XY: 0.236 AC XY: 1684 AN XY: 7130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.191 AC: 28994 AN: 151924 Hom.: 2963 Cov.: 31 AF XY: 0.189 AC XY: 14053 AN XY: 74244

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0460

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.175

Alfa AF: 0.205 Hom.: 837

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
DANN	Benign	0.49

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: rs1044386; hg19: chr19-4795289;