dbSNP rs201696967: FAM86B2:p.Val280Met (chr8-12427711-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001137610.3(FAM86B2):c.838G>A(p.Val280Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,094,726 control chromosomes in the GnomAD database, including 172 homozygotes. 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 0.00021 ( 4 hom., cov: 13)

Exomes 𝑓: 0.00051 ( 168 hom. )

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.761

Publications

0 publications found

Variant links:

Genes affected

FAM86B2 (HGNC:32222): (family with sequence similarity 86 member B2) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM86B2 links:

FAM66A (HGNC:30444): (family with sequence similarity 66 member A)

FAM66A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09697819).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137610.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	NM_001137610.3	MANE Select	c.838G>A	p.Val280Met	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.527G>A		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.446G>A		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.838G>A	p.Val280Met	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.808G>A	p.Val270Met	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.736G>A	p.Val246Met	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

95342

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000234

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000779

AC:

AN:

166928

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.000644

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000408

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000508

AC:

508

AN:

999384

Hom.:

168

Cov.:

AF XY:

0.000543

AC XY:

271

AN XY:

498690

show subpopulations

African (AFR)

AF:

0.000658

AC:

AN:

25854

American (AMR)

AF:

0.0000631

AC:

AN:

31710

Ashkenazi Jewish (ASJ)

AF:

0.0000627

AC:

AN:

15952

East Asian (EAS)

AF:

0.00

AC:

AN:

30388

South Asian (SAS)

AF:

0.0000774

AC:

AN:

64630

European-Finnish (FIN)

AF:

0.0000644

AC:

AN:

31066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3052

European-Non Finnish (NFE)

AF:

0.000627

AC:

473

AN:

754778

Other (OTH)

AF:

0.000191

AC:

AN:

41954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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

100

<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:

0.000210

AC:

AN:

95342

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

45920

show subpopulations

African (AFR)

AF:

0.000696

AC:

AN:

27318

American (AMR)

AF:

0.00

AC:

AN:

8818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1998

East Asian (EAS)

AF:

0.00

AC:

AN:

3584

South Asian (SAS)

AF:

0.00

AC:

AN:

2928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

42824

Other (OTH)

AF:

0.00

AC:

AN:

1202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000422

Hom.:

ExAC

AF:

0.000103

AC:

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

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.82

M_CAP

Benign

0.011

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

-0.76

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.0

REVEL

Benign

0.064

Sift

Uncertain

0.026

Sift4G

Uncertain

0.0060

Polyphen

0.61

Vest4

0.46

MutPred

0.64

Gain of sheet (P = 0.0344)

MVP

0.082

MPC

1.8

ClinPred

0.032

GERP RS

-0.54

Varity_R

0.10

gMVP

0.61

Mutation Taster

=100/0

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