11-111356445-T-C

Variant names:

• chr11-111356445-T-C
• rs4387383
• NM_006235.3:c.456+1000A>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.456+1000A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,928 control chromosomes in the GnomAD database, including 22,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22284 hom., cov: 31)
• Consequence: POU2AF1 NM_006235.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37
• Publications: 2 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=-0.89).
• BP6: Variant 11-111356445-T-C is Benign according to our data. Variant chr11-111356445-T-C is described in ClinVar as Benign. ClinVar VariationId is 2687959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 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.456+1000A>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.456+1000A>G		intron	N/A	ENSP00000376786.3	Q16633
	POU2AF1	ENST00000525584.1	TSL:3	n.575+1000A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79396 AN: 151810 Hom.: 22273 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.523 AC: 79428 AN: 151928 Hom.: 22284 Cov.: 31 AF XY: 0.520 AC XY: 38609 AN XY: 74242

African (AFR) AF: 0.327 AC: 13539 AN: 41402

American (AMR) AF: 0.629 AC: 9613 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1624 AN: 5156

South Asian (SAS) AF: 0.413 AC: 1987 AN: 4810

European-Finnish (FIN) AF: 0.575 AC: 6060 AN: 10534

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42960 AN: 67962

Other (OTH) AF: 0.556 AC: 1175 AN: 2112

Alfa AF: 0.571 Hom.: 4130

Bravo AF: 0.522

Asia WGS AF: 0.349 AC: 1216 AN: 3476

ClinVar

ClinVar submissions as Germline

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	-0.89
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4387383; hg19: chr11-111227170;