rs2942347

Variant names:

• chr10-5926107-A-C
• rs2942347
• NM_178150.3:c.2722+615A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178150.3(FBH1):​c.2722+615A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000802 in 124,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000080 (0 hom., cov: 32)
• Consequence: FBH1 NM_178150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 0 publications found

Genes affected

FBH1 (HGNC:13620): (F-box DNA helicase 1) This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178150.3. 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
	FBH1	NM_178150.3	MANE Select	c.2722+615A>C		intron	N/A	NP_835363.1	Q8NFZ0-1
	FBH1	NM_032807.5		c.2875+615A>C		intron	N/A	NP_116196.3
	FBH1	NM_001258452.2		c.2551+615A>C		intron	N/A	NP_001245381.1	F6UZG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBH1	ENST00000362091.9	TSL:1 MANE Select	c.2722+615A>C		intron	N/A	ENSP00000355415.4	Q8NFZ0-1
	FBH1	ENST00000379999.6	TSL:1	c.2875+615A>C		intron	N/A	ENSP00000369335.5	Q8NFZ0-2
	FBH1	ENST00000908866.1		c.2722+615A>C		intron	N/A	ENSP00000578925.1

Frequencies

GnomAD3 genomes AF: 0.00000802 AC: 1 AN: 124666 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000931

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000802 AC: 1 AN: 124734 Hom.: 0 Cov.: 32 AF XY: 0.0000166 AC XY: 1 AN XY: 60070

African (AFR) AF: 0.00 AC: 0 AN: 39362

American (AMR) AF: 0.0000931 AC: 1 AN: 10738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2916

East Asian (EAS) AF: 0.00 AC: 0 AN: 2900

South Asian (SAS) AF: 0.00 AC: 0 AN: 3514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54880

Other (OTH) AF: 0.00 AC: 0 AN: 1794

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.38
PhyloP100		-1.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2942347;

hg19: chr10-5968070;