Genetic Variant NM_001368135.1:c.*4256T>C (chr17-18668053-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001368135.1(FOXO3B):c.*4256T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,132 control chromosomes in the GnomAD database, including 22,288 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 0.54 ( 22275 hom., cov: 31)

Exomes 𝑓: 0.54 ( 13 hom. )

Consequence

FOXO3B
NM_001368135.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.198

Publications

12 publications found

Variant links:

Genes affected

FOXO3B (HGNC:3822): (forkhead box O3B) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FOXO3B links:

ZNF286B (HGNC:):

ZNF286B links:

ZNF286B (HGNC:33241): (zinc finger protein 286B (pseudogene)) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF286B 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=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOXO3B	NM_001368135.1 link	c.*4256T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000395675.7	NP_001355064.1
FOXO3B	NM_001368134.1 link	c.*4256T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001355063.1
ZNF286B	NR_160540.1 link	n.433-4826T>C	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXO3B	ENST00000395675.7 link	c.*4256T>C	3_prime_UTR_variant	Exon 4 of 4	6	NM_001368135.1	ENSP00000499455.1	A0A2Z4LIS9
ZNF286B	ENST00000285274.9 link	n.347-4826T>C	intron_variant	Intron 3 of 3	3
ZNF286B	ENST00000668878.2 link	n.322-4826T>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81893

AN:

151930

Hom.:

22228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.536

AC:

AN:

Hom.:

Cov.:

AF XY:

0.583

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.530

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.539

AC:

82003

AN:

152048

Hom.:

22275

Cov.:

AF XY:

0.537

AC XY:

39900

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.590

AC:

24473

AN:

41474

American (AMR)

AF:

0.528

AC:

8073

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1802

AN:

3470

East Asian (EAS)

AF:

0.400

AC:

2060

AN:

5148

South Asian (SAS)

AF:

0.435

AC:

2096

AN:

4820

European-Finnish (FIN)

AF:

0.583

AC:

6161

AN:

10572

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.523

AC:

35571

AN:

67956

Other (OTH)

AF:

0.548

AC:

1159

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1963

3926

5890

7853

9816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.530

Hom.:

66167

Bravo

AF:

0.540

Asia WGS

AF:

0.430

AC:

1498

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.4

(source)

DANN

Benign

0.29

PhyloP100

0.20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over