11-111358745-T-C

Variant names:

• chr11-111358745-T-C
• rs12282082
• NM_006235.3:c.147+43A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• agammaglobulinemia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF1	NM_006235.3	MANE Select	c.147+43A>G		intron	N/A	NP_006226.2	Q16633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF1	ENST00000393067.8	TSL:1 MANE Select	c.147+43A>G		intron	N/A	ENSP00000376786.3	Q16633
	POU2AF1	ENST00000531398.1	TSL:4	c.153+43A>G		intron	N/A	ENSP00000433527.1	E9PKH4
	POU2AF1	ENST00000525584.1	TSL:3	n.266+43A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.693 AC: 103458 AN: 149266 Hom.: 36125 Cov.: 30

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

GnomAD2 exomes AF: 0.677 AC: 101463 AN: 149898 AF XY: 0.663

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 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.: 33 AF XY: 0.710 AC XY: 485626 AN XY: 683574

African (AFR) AF: 0.589 AC: 18536 AN: 31488

American (AMR) AF: 0.819 AC: 29599 AN: 36132

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 19014 AN: 25164

East Asian (EAS) AF: 0.409 AC: 14657 AN: 35838

South Asian (SAS) AF: 0.481 AC: 38261 AN: 79494

European-Finnish (FIN) AF: 0.676 AC: 25263 AN: 37348

Middle Eastern (MID) AF: 0.682 AC: 3762 AN: 5520

European-Non Finnish (NFE) AF: 0.748 AC: 803509 AN: 1074540

Other (OTH) AF: 0.699 AC: 40413 AN: 57804

GnomAD4 genome AF: 0.693 AC: 103530 AN: 149392 Hom.: 36145 Cov.: 30 AF XY: 0.687 AC XY: 50129 AN XY: 72940

African (AFR) AF: 0.618 AC: 24969 AN: 40410

American (AMR) AF: 0.791 AC: 11958 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2598 AN: 3436

East Asian (EAS) AF: 0.422 AC: 2034 AN: 4820

South Asian (SAS) AF: 0.485 AC: 2246 AN: 4632

European-Finnish (FIN) AF: 0.670 AC: 6951 AN: 10372

Middle Eastern (MID) AF: 0.736 AC: 206 AN: 280

European-Non Finnish (NFE) AF: 0.748 AC: 50341 AN: 67330

Other (OTH) AF: 0.721 AC: 1500 AN: 2080

Alfa AF: 0.715 Hom.: 6008

Bravo AF: 0.696

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-2.0
Mutation Taster		=13/87	disease causing

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

Other links and lift over

dbSNP: rs12282082; hg19: chr11-111229470; COSMIC: COSV67576861; COSMIC: COSV67576861;