NM_001008777.3:c.626A>G

Variant names:

• chr17-38945127-T-C
• rs9906595
• NM_001008777.3:c.626A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008777.3(FBXO47):​c.626A>G​(p.Gln209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,610,356 control chromosomes in the GnomAD database, including 700,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68683 hom., cov: 30)
  • Exomes 𝑓: 0.93 (631772 hom.)
• Consequence: FBXO47 NM_001008777.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.10
• Publications: 32 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.728229E-7).
• BP6: Variant 17-38945127-T-C is Benign according to our data. Variant chr17-38945127-T-C is described in ClinVar as Benign. ClinVar VariationId is 1247558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO47	NM_001008777.3	MANE Select	c.626A>G	p.Gln209Arg	missense	Exon 7 of 11	NP_001008777.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO47	ENST00000378079.3	TSL:1 MANE Select	c.626A>G	p.Gln209Arg	missense	Exon 7 of 11	ENSP00000367319.2

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144382 AN: 152070 Hom.: 68622 Cov.: 30

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.936

GnomAD2 exomes AF: 0.949 AC: 238273 AN: 250958 AF XY: 0.949

Gnomad AFR exome AF: 0.988

Gnomad AMR exome AF: 0.958

Gnomad ASJ exome AF: 0.939

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.961

Gnomad NFE exome AF: 0.923

Gnomad OTH exome AF: 0.938

GnomAD4 exome AF: 0.930 AC: 1356776 AN: 1458168 Hom.: 631772 Cov.: 32 AF XY: 0.932 AC XY: 675719 AN XY: 725408

African (AFR) AF: 0.989 AC: 33046 AN: 33426

American (AMR) AF: 0.956 AC: 42688 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 24424 AN: 26080

East Asian (EAS) AF: 1.00 AC: 39640 AN: 39644

South Asian (SAS) AF: 0.984 AC: 84785 AN: 86122

European-Finnish (FIN) AF: 0.962 AC: 51350 AN: 53388

Middle Eastern (MID) AF: 0.944 AC: 5435 AN: 5760

European-Non Finnish (NFE) AF: 0.919 AC: 1018787 AN: 1108842

Other (OTH) AF: 0.940 AC: 56621 AN: 60250

GnomAD4 genome AF: 0.950 AC: 144503 AN: 152188 Hom.: 68683 Cov.: 30 AF XY: 0.953 AC XY: 70902 AN XY: 74404

African (AFR) AF: 0.986 AC: 40958 AN: 41546

American (AMR) AF: 0.941 AC: 14351 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3272 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5182

South Asian (SAS) AF: 0.987 AC: 4760 AN: 4824

European-Finnish (FIN) AF: 0.963 AC: 10198 AN: 10594

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62636 AN: 68010

Other (OTH) AF: 0.936 AC: 1976 AN: 2110

Alfa AF: 0.931 Hom.: 186867

Bravo AF: 0.949

TwinsUK AF: 0.923 AC: 3421

ALSPAC AF: 0.919 AC: 3543

ESP6500AA AF: 0.985 AC: 4338

ESP6500EA AF: 0.920 AC: 7914

ExAC AF: 0.950 AC: 115393

Asia WGS AF: 0.988 AC: 3438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30679340)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.062	T
MetaRNN	Benign	5.7e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.0	N
PhyloP100		2.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.055
Sift	Benign	0.80	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.074
ClinPred		0.0019	T
GERP RS		3.5
Varity_R		0.048
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9906595; hg19: chr17-37101380; COSMIC: COSV107482978;