rs376373414

Variant names:

• chr7-5501063-G-A
• rs376373414
• NM_024963.6:c.1206C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024963.6(FBXL18):​c.1206C>T​(p.Gly402Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,610,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (7 hom.)
• Consequence: FBXL18 NM_024963.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669
• Publications: 1 publications found

Genes affected

FBXL18 (HGNC:21874): (F-box and leucine rich repeat protein 18) The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP6: Variant 7-5501063-G-A is Benign according to our data. Variant chr7-5501063-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.669 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024963.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL18	NM_024963.6	MANE Select	c.1206C>T	p.Gly402Gly	synonymous	Exon 3 of 5	NP_079239.3
	FBXL18	NM_001321213.2		c.1206C>T	p.Gly402Gly	synonymous	Exon 3 of 5	NP_001308142.1	Q96ME1-5
	FBXL18	NM_001363441.2		c.1206C>T	p.Gly402Gly	synonymous	Exon 3 of 5	NP_001350370.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL18	ENST00000382368.8	TSL:5 MANE Select	c.1206C>T	p.Gly402Gly	synonymous	Exon 3 of 5	ENSP00000371805.3	Q96ME1-4
	FBXL18	ENST00000458142.1	TSL:2	c.855C>T	p.Gly285Gly	synonymous	Exon 1 of 3	ENSP00000405896.1	A0A994ENR3
	FBXL18	ENST00000948868.1		c.987C>T	p.Gly329Gly	synonymous	Exon 2 of 4	ENSP00000618927.1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152264 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00232 AC: 556 AN: 239146 AF XY: 0.00237

Gnomad AFR exome AF: 0.000681

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.0271

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.00683

GnomAD4 exome AF: 0.00125 AC: 1828 AN: 1457772 Hom.: 7 Cov.: 30 AF XY: 0.00129 AC XY: 939 AN XY: 725264

African (AFR) AF: 0.00102 AC: 34 AN: 33458

American (AMR) AF: 0.00291 AC: 130 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 657 AN: 26052

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50510

Middle Eastern (MID) AF: 0.0164 AC: 94 AN: 5736

European-Non Finnish (NFE) AF: 0.000605 AC: 672 AN: 1111274

Other (OTH) AF: 0.00348 AC: 210 AN: 60288

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152380 Hom.: 1 Cov.: 33 AF XY: 0.00178 AC XY: 133 AN XY: 74520

African (AFR) AF: 0.000577 AC: 24 AN: 41596

American (AMR) AF: 0.00294 AC: 45 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000808 AC: 55 AN: 68036

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00339 Hom.: 1

Bravo AF: 0.00201

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00267

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

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: rs376373414; hg19: chr7-5540694; COSMIC: COSV66667742; COSMIC: COSV66667742;