dbSNP rs12282082: POU2AF1:c.147+43A>G (chr11-111358745-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006235.3(POU2AF1):c.147+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,532,720 control chromosomes in the GnomAD database, including 397,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 36145 hom., cov: 30)

Exomes 𝑓: 0.72 ( 361293 hom. )

Consequence

POU2AF1
NM_006235.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02

Variant links:

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-111358745-T-C is Benign according to our data. Variant chr11-111358745-T-C is described in ClinVar as [Benign]. Clinvar id is 2688040.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF1	NM_006235.3 link	c.147+43A>G		intron_variant	Intron 2 of 4	ENST00000393067.8	NP_006226.2	Q16633

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000393067.8 link	c.147+43A>G		intron_variant	Intron 2 of 4	1	NM_006235.3	ENSP00000376786.3		Q16633

Frequencies

GnomAD3 genomes

AF:

0.693

AC:

103458

AN:

149266

Hom.:

36125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.801

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.738

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.723

GnomAD3 exomes

AF:

0.677

AC:

101463

AN:

149898

Hom.:

35696

AF XY:

0.663

AC XY:

52799

AN XY:

79666

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.750

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.661

Gnomad NFE exome

AF:

0.741

Gnomad OTH exome

AF:

0.719

GnomAD4 exome

AF:

0.718

AC:

993014

AN:

1383328

Hom.:

361293

Cov.:

AF XY:

0.710

AC XY:

485626

AN XY:

683574

show subpopulations

Gnomad4 AFR exome

AF:

0.589

Gnomad4 AMR exome

AF:

0.819

Gnomad4 ASJ exome

AF:

0.756

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.676

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.699

GnomAD4 genome

AF:

0.693

AC:

103530

AN:

149392

Hom.:

36145

Cov.:

AF XY:

0.687

AC XY:

50129

AN XY:

72940

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.791

Gnomad4 ASJ

AF:

0.756

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.485

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.748

Gnomad4 OTH

AF:

0.721

Alfa

AF:

0.718

Hom.:

5858

Bravo

AF:

0.696

Asia WGS

AF:

0.421

AC:

1466

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

DANN

Benign

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over