rs256940

Positions:

• chr5-115530494-G-A
• chr5-115530494-G-C

Variant summary

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

The NM_020177.3(FEM1C):​c.545-4877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,076 control chromosomes in the GnomAD database, including 43,751 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 0.75 (43751 hom., cov: 32)
• Consequence: FEM1C NM_020177.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

Genes affected

FEM1C (HGNC:16933): (fem-1 homolog C) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in cytosol and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.545-4877C>T		intron_variant		ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.545-4877C>T		intron_variant		1	NM_020177.3	ENSP00000274457	P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113682 AN: 151958 Hom.: 43696 Cov.: 32

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.737

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.748 AC: 113787 AN: 152076 Hom.: 43751 Cov.: 32 AF XY: 0.747 AC XY: 55521 AN XY: 74324

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.731

Alfa AF: 0.694 Hom.: 11644

Bravo AF: 0.746

Asia WGS AF: 0.624 AC: 2176 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	0.63
DANN	Benign	0.47

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: rs256940; hg19: chr5-114866191; COSMIC: COSV57231093;