rs372702

Variant names:

• chr5-115526911-G-A
• rs372702
• NM_020177.3:c.545-1294C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-115526911-G-A
• chr5-115526911-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.545-1294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,754 control chromosomes in the GnomAD database, including 27,002 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 0.59 (27002 hom., cov: 31)
• Consequence: FEM1C NM_020177.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.545-1294C>T		intron_variant	Intron 2 of 2	ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.545-1294C>T		intron_variant	Intron 2 of 2	1	NM_020177.3	ENSP00000274457.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89492 AN: 151636 Hom.: 26979 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.590 AC: 89553 AN: 151754 Hom.: 27002 Cov.: 31 AF XY: 0.587 AC XY: 43538 AN XY: 74152

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.571

Alfa AF: 0.556 Hom.: 2964

Bravo AF: 0.605

Asia WGS AF: 0.685 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.36

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: rs372702; hg19: chr5-114862608;