1-16315404-C-T

Variant names:

• chr1-16315404-C-T
• rs2273311
• NM_018994.3:c.15G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018994.3(FBXO42):​c.15G>A​(p.Ser5Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,610 control chromosomes in the GnomAD database, including 127,500 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 0.33 (9851 hom., cov: 31)
  • Exomes 𝑓: 0.39 (117649 hom.)
• Consequence: FBXO42 NM_018994.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 23 publications found

Genes affected

FBXO42 (HGNC:29249): (F-box protein 42) Members of the F-box protein family, such as FBXO42, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (SKP1A; MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018994.3. 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
	FBXO42	NM_018994.3	MANE Select	c.15G>A	p.Ser5Ser	synonymous	Exon 2 of 10	NP_061867.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO42	ENST00000375592.8	TSL:1 MANE Select	c.15G>A	p.Ser5Ser	synonymous	Exon 2 of 10	ENSP00000364742.3
	FBXO42	ENST00000478089.1	TSL:1	n.-37G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49880 AN: 151910 Hom.: 9860 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.403 AC: 101000 AN: 250818 AF XY: 0.406

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.398

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.392 AC: 573422 AN: 1461582 Hom.: 117649 Cov.: 39 AF XY: 0.393 AC XY: 285798 AN XY: 727098

African (AFR) AF: 0.0960 AC: 3214 AN: 33480

American (AMR) AF: 0.359 AC: 16046 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 9425 AN: 26132

East Asian (EAS) AF: 0.700 AC: 27776 AN: 39688

South Asian (SAS) AF: 0.392 AC: 33837 AN: 86228

European-Finnish (FIN) AF: 0.508 AC: 27152 AN: 53416

Middle Eastern (MID) AF: 0.346 AC: 1992 AN: 5764

European-Non Finnish (NFE) AF: 0.387 AC: 430322 AN: 1111796

Other (OTH) AF: 0.392 AC: 23658 AN: 60374

GnomAD4 genome AF: 0.328 AC: 49866 AN: 152028 Hom.: 9851 Cov.: 31 AF XY: 0.336 AC XY: 24963 AN XY: 74302

African (AFR) AF: 0.109 AC: 4513 AN: 41494

American (AMR) AF: 0.336 AC: 5130 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3483 AN: 5168

South Asian (SAS) AF: 0.397 AC: 1910 AN: 4812

European-Finnish (FIN) AF: 0.512 AC: 5401 AN: 10558

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26948 AN: 67958

Other (OTH) AF: 0.336 AC: 711 AN: 2114

Alfa AF: 0.363 Hom.: 32209

Bravo AF: 0.309

Asia WGS AF: 0.466 AC: 1617 AN: 3478

EpiCase AF: 0.402

EpiControl AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2273311; hg19: chr1-16641899; COSMIC: COSV65044676; COSMIC: COSV65044676;