17-38943728-C-A

Variant names:

• chr17-38943728-C-A
• rs148926547
• NM_001008777.3:c.802G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001008777.3(FBXO47):​c.802G>T​(p.Val268Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,605,444 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: FBXO47 NM_001008777.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.124
• Publications: 2 publications found

Genes affected

FBXO47 (HGNC:31969): (F-box protein 47)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010122001).
• BP6: Variant 17-38943728-C-A is Benign according to our data. Variant chr17-38943728-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3049241.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008777.3. 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
	FBXO47	NM_001008777.3	MANE Select	c.802G>T	p.Val268Phe	missense	Exon 8 of 11	NP_001008777.2	Q5MNV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO47	ENST00000378079.3	TSL:1 MANE Select	c.802G>T	p.Val268Phe	missense	Exon 8 of 11	ENSP00000367319.2	Q5MNV8

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00809

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000482 AC: 117 AN: 242550 AF XY: 0.000266

Gnomad AFR exome AF: 0.00691

Gnomad AMR exome AF: 0.000224

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000218 AC: 317 AN: 1453170 Hom.: 3 Cov.: 30 AF XY: 0.000191 AC XY: 138 AN XY: 722840

African (AFR) AF: 0.00813 AC: 267 AN: 32836

American (AMR) AF: 0.000191 AC: 8 AN: 41860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 84364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109592

Other (OTH) AF: 0.000666 AC: 40 AN: 60104

GnomAD4 genome AF: 0.00227 AC: 346 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74462

African (AFR) AF: 0.00811 AC: 337 AN: 41538

American (AMR) AF: 0.000392 AC: 6 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000825 Hom.: 2

Bravo AF: 0.00261

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000659 AC: 80

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000549

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FBXO47-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.12
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.037
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.39
MVP		0.32
MPC		0.091
ClinPred		0.0090	T
GERP RS		-3.9
Varity_R		0.078
gMVP		0.44
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs148926547; hg19: chr17-37099981;