11-111356445-T-C

Variant names:

• chr11-111356445-T-C
• rs4387383
• NM_006235.3:c.456+1000A>G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF1	NM_006235.3	c.456+1000A>G		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+1000A>G		intron_variant	Intron 4 of 4	1	NM_006235.3	ENSP00000376786.3
POU2AF1	ENST00000525584.1	n.575+1000A>G		intron_variant	Intron 4 of 4	3

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.556

Alfa AF: 0.578 Hom.: 4076

Bravo AF: 0.522

Asia WGS AF: 0.349 AC: 1216 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs4387383; hg19: chr11-111227170;