dbSNP rs2296129: FAM209B:p.Glu129Ala (chr20-56536308-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001013646.4(FAM209B):c.386A>C(p.Glu129Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,613,934 control chromosomes in the GnomAD database, including 5,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.023 ( 563 hom., cov: 32)

Exomes 𝑓: 0.018 ( 4549 hom. )

Consequence

FAM209B
NM_001013646.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

15 publications found

Variant links:

Genes affected

FAM209B (HGNC:16101): (family with sequence similarity 209 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209B 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 (MetaRNN=3.3432245E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM209B	NM_001013646.4 link	c.386A>C	p.Glu129Ala	missense_variant	Exon 2 of 2	ENST00000371325.1	NP_001013668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1 link	c.386A>C	p.Glu129Ala	missense_variant	Exon 2 of 2	1	NM_001013646.4	ENSP00000360376.1

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3438

AN:

152136

Hom.:

560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.0467

AC:

11730

AN:

251200

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.00750

Gnomad AMR exome

AF:

0.0502

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.0256

GnomAD4 exome

AF:

0.0176

AC:

25768

AN:

1461680

Hom.:

4549

Cov.:

AF XY:

0.0174

AC XY:

12623

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.00693

AC:

232

AN:

33476

American (AMR)

AF:

0.0480

AC:

2142

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00249

AC:

AN:

26132

East Asian (EAS)

AF:

0.464

AC:

18415

AN:

39690

South Asian (SAS)

AF:

0.0256

AC:

2203

AN:

86196

European-Finnish (FIN)

AF:

0.000973

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000828

AC:

921

AN:

1111946

Other (OTH)

AF:

0.0280

AC:

1691

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

923

1847

2770

3694

4617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.0226

AC:

3446

AN:

152254

Hom.:

563

Cov.:

AF XY:

0.0257

AC XY:

1913

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00820

AC:

341

AN:

41564

American (AMR)

AF:

0.0273

AC:

417

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.459

AC:

2369

AN:

5160

South Asian (SAS)

AF:

0.0371

AC:

179

AN:

4822

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

68008

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

119

238

358

477

596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0181

Hom.:

1201

Bravo

AF:

0.0274

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0443

AC:

5383

Asia WGS

AF:

0.182

AC:

629

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0040

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.54

MetaRNN

Benign

0.00033

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

REVEL

Benign

0.076

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.013

Polyphen

0.0010

Vest4

0.060

MPC

0.51

ClinPred

0.016

GERP RS

1.2

Varity_R

0.085

gMVP

0.11

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over