dbSNP rs10891246: POU2AF3:p.Thr13Ala (chr11-111299815-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 ENST00000638573.1(POU2AF3):c.37A>G(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 948,442 control chromosomes in the GnomAD database, including 239,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 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 0.72 ( 40112 hom., cov: 33)

Exomes 𝑓: 0.71 ( 199513 hom. )

Consequence

POU2AF3
ENST00000638573.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Publications

11 publications found

Variant links:

Genes affected

POU2AF3 (HGNC:26978): (POU class 2 homeobox associating factor 3) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF3 links:

COLCA1 (HGNC:33789): (colorectal cancer associated 1) This gene encodes a transmembrane protein that localizes to granular structures, including crystalloid eosinophilic granules and other granular organelles. This gene, along with an overlapping opposite strand gene, has been implicated as a susceptibility locus for colorectal cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

COLCA1 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=0.0030952394).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2 link	c.8-712A>G		intron_variant	Intron 1 of 4	ENST00000610738.6	NP_001258387.1	A8K830-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6 link	c.8-712A>G		intron_variant	Intron 1 of 4	1	NM_001271458.2	ENSP00000484135.1		A8K830-5

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110187

AN:

152040

Hom.:

40077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.725

GnomAD4 exome

AF:

0.706

AC:

561861

AN:

796284

Hom.:

199513

Cov.:

AF XY:

0.707

AC XY:

270303

AN XY:

382236

show subpopulations

African (AFR)

AF:

0.714

AC:

12487

AN:

17500

American (AMR)

AF:

0.795

AC:

6445

AN:

8110

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

9007

AN:

12614

East Asian (EAS)

AF:

0.650

AC:

16425

AN:

25282

South Asian (SAS)

AF:

0.830

AC:

11620

AN:

14004

European-Finnish (FIN)

AF:

0.763

AC:

16141

AN:

21168

Middle Eastern (MID)

AF:

0.785

AC:

1919

AN:

2446

European-Non Finnish (NFE)

AF:

0.701

AC:

463267

AN:

660558

Other (OTH)

AF:

0.709

AC:

24550

AN:

34602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8383

16767

25150

33534

41917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12450

24900

37350

49800

62250

<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:

0.725

AC:

110274

AN:

152158

Hom.:

40112

Cov.:

AF XY:

0.728

AC XY:

54175

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.712

AC:

29578

AN:

41524

American (AMR)

AF:

0.783

AC:

11975

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2519

AN:

3472

East Asian (EAS)

AF:

0.593

AC:

3059

AN:

5158

South Asian (SAS)

AF:

0.827

AC:

3995

AN:

4828

European-Finnish (FIN)

AF:

0.772

AC:

8190

AN:

10606

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.716

AC:

48676

AN:

67958

Other (OTH)

AF:

0.730

AC:

1541

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1629

3258

4886

6515

8144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.730

Hom.:

12680

Bravo

AF:

0.720

TwinsUK

AF:

0.701

AC:

2599

ALSPAC

AF:

0.706

AC:

2721

Asia WGS

AF:

0.761

AC:

2647

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.7

(source)

DANN

Benign

0.59

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0031

PhyloP100

0.017

GERP RS

-5.7

PromoterAI

-0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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