19-4796770-A-G

Position:

• chr19-4796770-A-G

Variant summary

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

The NM_018708.3(FEM1A):​c.*2906A>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 0.485 in 152,238 control chromosomes in the GnomAD database, including 18,430 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 0.48 (18387 hom., cov: 32)
  • Exomes 𝑓: 0.57 (43 hom.)
• Consequence: FEM1A NM_018708.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1A	NM_018708.3	c.*2906A>G		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.*2906A>G		3_prime_UTR_variant	1/1	6	NM_018708.3	ENSP00000269856.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73615 AN: 151880 Hom.: 18386 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.567 AC: 136 AN: 240 Hom.: 43 Cov.: 0 AF XY: 0.556 AC XY: 100 AN XY: 180

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.484 AC: 73638 AN: 151998 Hom.: 18387 Cov.: 32 AF XY: 0.485 AC XY: 36067 AN XY: 74292

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.484

Alfa AF: 0.521 Hom.: 34968

Bravo AF: 0.467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.044
DANN	Benign	0.091

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: rs4806998; hg19: chr19-4796782;