19-4796770-A-G

Variant names:

• chr19-4796770-A-G
• rs4806998
• NM_018708.3:c.*2906A>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.*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
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1A	NM_018708.3	MANE Select	c.*2906A>G		3_prime_UTR	Exon 1 of 1	NP_061178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1A	ENST00000269856.5	TSL:6 MANE Select	c.*2906A>G		3_prime_UTR	Exon 1 of 1	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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 2 AN: 6

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.571 AC: 8 AN: 14

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.582 AC: 114 AN: 196

Other (OTH) AF: 0.625 AC: 5 AN: 8

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

African (AFR) AF: 0.362 AC: 15023 AN: 41496

American (AMR) AF: 0.467 AC: 7116 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2995 AN: 5154

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6647 AN: 10560

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36669 AN: 67956

Other (OTH) AF: 0.484 AC: 1021 AN: 2108

Alfa AF: 0.509 Hom.: 58490

Bravo AF: 0.467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.044
DANN	Benign	0.091
PhyloP100		-2.4

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

Other links and lift over

dbSNP: rs4806998; hg19: chr19-4796782;