ENST00000440067.4:c.765+7768T>C

Variant names:

• chr7-103017295-A-G
• rs4486110
• NM_001394494.2:c.765+7768T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000440067.4(FBXL13):​c.765+7768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.30 (7177 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: FBXL13 ENST00000440067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 0 publications found

Genes affected

FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (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, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440067.4. 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
	FBXL13	NM_001394494.2	MANE Select	c.765+7768T>C		intron	N/A	NP_001381423.1	C9JI88
	FBXL13	NM_145032.3		c.495+7768T>C		intron	N/A	NP_659469.3	Q8N1P0
	FBXL13	NM_001287150.2		c.495+7768T>C		intron	N/A	NP_001274079.1	Q8NEE6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.765+7768T>C		intron	N/A	ENSP00000390126.2	C9JI88
	FBXL13	ENST00000379305.7	TSL:1	n.*494+7768T>C		intron	N/A	ENSP00000368607.4	A0A8V8NC12
	FBXL13	ENST00000448002.6	TSL:1	n.765+7768T>C		intron	N/A	ENSP00000405434.2	E7ERH8

Frequencies

GnomAD3 genomes AF: 0.304 AC: 44219 AN: 145688 Hom.: 7158 Cov.: 28

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.273

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.304 AC: 44272 AN: 145804 Hom.: 7177 Cov.: 28 AF XY: 0.304 AC XY: 21558 AN XY: 70910

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.297 AC: 11502 AN: 38788

American (AMR) AF: 0.291 AC: 4247 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 893 AN: 3394

East Asian (EAS) AF: 0.580 AC: 2846 AN: 4908

South Asian (SAS) AF: 0.424 AC: 1901 AN: 4482

European-Finnish (FIN) AF: 0.251 AC: 2529 AN: 10060

Middle Eastern (MID) AF: 0.308 AC: 88 AN: 286

European-Non Finnish (NFE) AF: 0.292 AC: 19385 AN: 66382

Other (OTH) AF: 0.280 AC: 565 AN: 2020

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.310 Hom.: 823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.26
PhyloP100		0.12
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: rs4486110; hg19: chr7-102657742;