NM_006235.3:c.16+5131T>C

Variant names:

• chr11-111374031-A-G
• rs12799202
• NM_006235.3:c.16+5131T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006235.3(POU2AF1):​c.16+5131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,736 control chromosomes in the GnomAD database, including 33,267 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 0.65 (33267 hom., cov: 30)
• Consequence: POU2AF1 NM_006235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF1	NM_006235.3	c.16+5131T>C		intron_variant	Intron 1 of 4	ENST00000393067.8	NP_006226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000393067.8	c.16+5131T>C		intron_variant	Intron 1 of 4	1	NM_006235.3	ENSP00000376786.3
POU2AF1	ENST00000531398.1	c.23-15113T>C		intron_variant	Intron 2 of 4	4		ENSP00000433527.1
POU2AF1	ENST00000526535.1	n.114+5131T>C		intron_variant	Intron 1 of 1	4
POU2AF1	ENST00000530793.5	n.193+3743T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98255 AN: 151616 Hom.: 33267 Cov.: 30

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.687

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98287 AN: 151736 Hom.: 33267 Cov.: 30 AF XY: 0.642 AC XY: 47609 AN XY: 74138

African (AFR) AF: 0.478 AC: 19747 AN: 41308

American (AMR) AF: 0.774 AC: 11795 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2537 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2091 AN: 5170

South Asian (SAS) AF: 0.436 AC: 2104 AN: 4822

European-Finnish (FIN) AF: 0.666 AC: 6944 AN: 10430

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50691 AN: 67978

Other (OTH) AF: 0.685 AC: 1445 AN: 2108

Alfa AF: 0.715 Hom.: 117896

Bravo AF: 0.653

Asia WGS AF: 0.406 AC: 1412 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.90
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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: rs12799202; hg19: chr11-111244756;