dbSNP rs2043031: FAM222B:p.Leu471Leu (chr17-28758546-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001077498.3(FAM222B):c.1413T>C(p.Leu471Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,610,036 control chromosomes in the GnomAD database, including 35,829 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 0.19 ( 2883 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32946 hom. )

Consequence

FAM222B
NM_001077498.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Publications

21 publications found

Variant links:

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM222B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-0.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM222B	NM_001077498.3 link	c.1413T>C	p.Leu471Leu	synonymous_variant	Exon 3 of 3	ENST00000581407.6	NP_001070966.1	Q8WU58A0A024QZ60B3KQ88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM222B	ENST00000581407.6 link	c.1413T>C	p.Leu471Leu	synonymous_variant	Exon 3 of 3	1	NM_001077498.3	ENSP00000462419.1		Q8WU58

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28869

AN:

152052

Hom.:

2878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.211

AC:

51640

AN:

244498

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.209

AC:

304464

AN:

1457868

Hom.:

32946

Cov.:

AF XY:

0.212

AC XY:

153782

AN XY:

725420

show subpopulations

African (AFR)

AF:

0.155

AC:

5197

AN:

33474

American (AMR)

AF:

0.212

AC:

9488

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

6291

AN:

26134

East Asian (EAS)

AF:

0.251

AC:

9955

AN:

39698

South Asian (SAS)

AF:

0.312

AC:

26889

AN:

86254

European-Finnish (FIN)

AF:

0.186

AC:

9257

AN:

49658

Middle Eastern (MID)

AF:

0.240

AC:

1383

AN:

5768

European-Non Finnish (NFE)

AF:

0.201

AC:

223601

AN:

1111824

Other (OTH)

AF:

0.206

AC:

12403

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16559

33117

49676

66234

82793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7898

15796

23694

31592

39490

<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:

0.190

AC:

28882

AN:

152168

Hom.:

2883

Cov.:

AF XY:

0.190

AC XY:

14164

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.147

AC:

6113

AN:

41524

American (AMR)

AF:

0.217

AC:

3320

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

814

AN:

3472

East Asian (EAS)

AF:

0.191

AC:

986

AN:

5162

South Asian (SAS)

AF:

0.307

AC:

1485

AN:

4830

European-Finnish (FIN)

AF:

0.187

AC:

1985

AN:

10590

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13508

AN:

67978

Other (OTH)

AF:

0.193

AC:

409

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1249

2498

3746

4995

6244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.198

Hom.:

6118

Bravo

AF:

0.189

Asia WGS

AF:

0.250

AC:

870

AN:

3478

EpiCase

AF:

0.196

EpiControl

AF:

0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

(source)

DANN

Benign

0.57

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(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

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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