chr19-4794245-T-G

Position:

• chr19-4794245-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1A	NM_018708.3	c.*381T>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.*381T>G		3_prime_UTR_variant	1/1		NM_018708.3	ENSP00000269856	P1
	ENST00000601192.1	n.1311A>C		non_coding_transcript_exon_variant	1/2	4

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

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.633

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

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.653

Alfa AF: 0.641 Hom.: 6677

Bravo AF: 0.651

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.37

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: rs11085099; hg19: chr19-4794257; COSMIC: COSV54164561; COSMIC: COSV54164561;