11-111356445-T-C

Position:

• chr11-111356445-T-C

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/exons	MANE	UniProt
POU2AF1	NM_006235.3	c.456+1000A>G		intron_variant		ENST00000393067.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2AF1	ENST00000393067.8	c.456+1000A>G		intron_variant		1	NM_006235.3	P1
POU2AF1	ENST00000525584.1	n.575+1000A>G		intron_variant, non_coding_transcript_variant		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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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;