NM_006235.3:c.456+1227C>T

Variant names:

• chr11-111356218-G-A
• rs4514461
• NM_006235.3:c.456+1227C>T

Variant summary

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

The NM_006235.3(POU2AF1):​c.456+1227C>T 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 152,076 control chromosomes in the GnomAD database, including 22,326 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 0.52 (22326 hom., cov: 32)
• Consequence: POU2AF1 NM_006235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.726
• Publications: 0 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF1	NM_006235.3	c.456+1227C>T		intron_variant	Intron 4 of 4	ENST00000393067.8	NP_006226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000393067.8	c.456+1227C>T		intron_variant	Intron 4 of 4	1	NM_006235.3	ENSP00000376786.3
POU2AF1	ENST00000525584.1	n.575+1227C>T		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79526 AN: 151958 Hom.: 22316 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.523 AC: 79559 AN: 152076 Hom.: 22326 Cov.: 32 AF XY: 0.520 AC XY: 38693 AN XY: 74344

African (AFR) AF: 0.329 AC: 13652 AN: 41462

American (AMR) AF: 0.629 AC: 9608 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3464

East Asian (EAS) AF: 0.314 AC: 1629 AN: 5182

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4814

European-Finnish (FIN) AF: 0.575 AC: 6085 AN: 10574

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

European-Non Finnish (NFE) AF: 0.632 AC: 42956 AN: 67990

Other (OTH) AF: 0.555 AC: 1170 AN: 2110

Alfa AF: 0.574 Hom.: 11629

Bravo AF: 0.522

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		0.73
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: rs4514461; hg19: chr11-111226943;