Genetic Variant OAF:p.Leu20Phe (chr11-120211337-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178507.4(OAF):c.58C>T(p.Leu20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,408,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

OAF
NM_178507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.483

Publications

0 publications found

Variant links:

Genes affected

OAF (HGNC:28752): (out at first homolog)

OAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.086643964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178507.4. 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
	OAF	NM_178507.4	MANE Select	c.58C>T	p.Leu20Phe	missense	Exon 1 of 4	NP_848602.1	Q86UD1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAF	ENST00000328965.9	TSL:1 MANE Select	c.58C>T	p.Leu20Phe	missense	Exon 1 of 4	ENSP00000332613.3	Q86UD1
OAF	ENST00000867027.1		c.58C>T	p.Leu20Phe	missense	Exon 1 of 3	ENSP00000537086.1
OAF	ENST00000531220.1	TSL:3	c.-207C>T		5_prime_UTR	Exon 1 of 4	ENSP00000431865.1	E9PJ29

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00

AC:

AN:

45860

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000597

AC:

AN:

1256900

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

617186

show subpopulations

African (AFR)

AF:

0.00198

AC:

AN:

24800

American (AMR)

AF:

0.0000570

AC:

AN:

17538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20196

East Asian (EAS)

AF:

0.00

AC:

AN:

27722

South Asian (SAS)

AF:

0.00

AC:

AN:

62658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36882

Middle Eastern (MID)

AF:

0.000263

AC:

AN:

3808

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

1011630

Other (OTH)

AF:

0.000135

AC:

AN:

51666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000513

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00179

AC:

AN:

41438

American (AMR)

AF:

0.000131

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67952

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000646

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.28

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-0.48

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.21

REVEL

Benign

0.069

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.81

Vest4

0.24

MutPred

0.24

Loss of disorder (P = 0.0377)

MVP

0.20

MPC

0.56

ClinPred

0.25

GERP RS

-0.94

PromoterAI

-0.0015

Neutral

(source)

Varity_R

0.038

gMVP

0.27

Mutation Taster

=65/35

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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