dbSNP rs17720191: FBXO38:c.963-477G>A (chr5-148410158-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_205836.3(FBXO38):c.963-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,522 control chromosomes in the GnomAD database, including 12,344 homozygotes. 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 0.38 ( 12323 hom., cov: 32)

Exomes 𝑓: 0.26 ( 21 hom. )

Consequence

FBXO38
NM_205836.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.176

Publications

3 publications found

Variant links:

Genes affected

FBXO38 (HGNC:28844): (F-box protein 38) This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

FBXO38 Gene-Disease associations (from GenCC):

neuronopathy, distal hereditary motor, type 2D
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
distal hereditary motor neuropathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
distal hereditary motor neuropathy type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FBXO38 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205836.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBXO38	NM_205836.3	MANE Select	c.963-477G>A	intron	N/A	NP_995308.1
FBXO38	NM_030793.5		c.963-477G>A	intron	N/A	NP_110420.3
FBXO38	NM_001271723.2		c.963-477G>A	intron	N/A	NP_001258652.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBXO38	ENST00000340253.10	TSL:5 MANE Select	c.963-477G>A	intron	N/A	ENSP00000342023.6
FBXO38	ENST00000394370.7	TSL:1	c.963-477G>A	intron	N/A	ENSP00000377895.3
FBXO38	ENST00000513826.1	TSL:1	c.963-477G>A	intron	N/A	ENSP00000426410.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58244

AN:

151804

Hom.:

12294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.343

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.349

GnomAD4 exome

AF:

0.263

AC:

158

AN:

600

Hom.:

AF XY:

0.268

AC XY:

AN XY:

314

show subpopulations

African (AFR)

AF:

0.650

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

AN:

East Asian (EAS)

AF:

0.700

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.188

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.234

AC:

102

AN:

436

Other (OTH)

AF:

0.344

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58321

AN:

151922

Hom.:

12323

Cov.:

AF XY:

0.390

AC XY:

29007

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.522

AC:

21625

AN:

41402

American (AMR)

AF:

0.427

AC:

6516

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1181

AN:

3466

East Asian (EAS)

AF:

0.668

AC:

3445

AN:

5158

South Asian (SAS)

AF:

0.395

AC:

1904

AN:

4820

European-Finnish (FIN)

AF:

0.335

AC:

3536

AN:

10562

Middle Eastern (MID)

AF:

0.338

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.278

AC:

18862

AN:

67924

Other (OTH)

AF:

0.355

AC:

751

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1741

3483

5224

6966

8707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.301

Hom.:

7522

Bravo

AF:

0.397

Asia WGS

AF:

0.546

AC:

1895

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.4

(source)

DANN

Benign

0.40

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over