rs12792445

Variant names:

• chr11-111305626-C-T
• rs12792445
• NM_001271458.2:c.157+644C>T

Variant summary

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

The NM_001271458.2(POU2AF3):​c.157+644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,048 control chromosomes in the GnomAD database, including 5,730 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 0.26 (5730 hom., cov: 32)
• Consequence: POU2AF3 NM_001271458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 3 publications found

Genes affected

POU2AF3 (HGNC:26978): (POU class 2 homeobox associating factor 3) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COLCA1 (HGNC:33789): (colorectal cancer associated 1) This gene encodes a transmembrane protein that localizes to granular structures, including crystalloid eosinophilic granules and other granular organelles. This gene, along with an overlapping opposite strand gene, has been implicated as a susceptibility locus for colorectal cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271458.2. 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
	POU2AF3	NM_001271458.2	MANE Select	c.157+644C>T		intron	N/A	NP_001258387.1	A8K830-5
	POU2AF3	NM_001136105.3		c.-135+644C>T		intron	N/A	NP_001129577.1	A8K830-1
	POU2AF3	NM_001271457.2		c.-135+644C>T		intron	N/A	NP_001258386.1	A8K830-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	ENST00000610738.6	TSL:1 MANE Select	c.157+644C>T		intron	N/A	ENSP00000484135.1	A8K830-5
	POU2AF3	ENST00000638573.1	TSL:1	c.262+644C>T		intron	N/A	ENSP00000492570.1	A8K830-4
	POU2AF3	ENST00000398035.6	TSL:1	c.-135+644C>T		intron	N/A	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39366 AN: 151930 Hom.: 5725 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.259 AC: 39387 AN: 152048 Hom.: 5730 Cov.: 32 AF XY: 0.264 AC XY: 19586 AN XY: 74284

African (AFR) AF: 0.134 AC: 5566 AN: 41490

American (AMR) AF: 0.267 AC: 4069 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3464

East Asian (EAS) AF: 0.442 AC: 2286 AN: 5170

South Asian (SAS) AF: 0.473 AC: 2276 AN: 4816

European-Finnish (FIN) AF: 0.314 AC: 3320 AN: 10562

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20050 AN: 67964

Other (OTH) AF: 0.273 AC: 576 AN: 2112

Alfa AF: 0.281 Hom.: 3506

Bravo AF: 0.246

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.37
PhyloP100		-0.061
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: rs12792445; hg19: chr11-111176351;