11-111299815-A-G

Variant names:

• chr11-111299815-A-G
• rs10891246
• ENST00000638573.1:c.37A>G

Variant summary

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

The ENST00000638573.1(POU2AF3):​c.37A>G​(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 948,442 control chromosomes in the GnomAD database, including 239,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40112 hom., cov: 33)
  • Exomes 𝑓: 0.71 (199513 hom.)
• Consequence: POU2AF3 ENST00000638573.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 11 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 (MetaRNN=0.0030952394).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638573.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	NM_001271458.2	MANE Select	c.8-712A>G		intron	N/A	NP_001258387.1
	POU2AF3	NM_001370484.1		c.-487A>G		5_prime_UTR	Exon 1 of 5	NP_001357413.1
	POU2AF3	NM_001136105.3		c.-285+91A>G		intron	N/A	NP_001129577.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	ENST00000638573.1	TSL:1	c.37A>G	p.Thr13Ala	missense	Exon 2 of 6	ENSP00000492570.1
	COLCA1	ENST00000355430.5	TSL:1	n.99T>C		non_coding_transcript_exon	Exon 1 of 2
	POU2AF3	ENST00000639470.1	TSL:1	n.37A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000492182.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110187 AN: 152040 Hom.: 40077 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.706 AC: 561861 AN: 796284 Hom.: 199513 Cov.: 10 AF XY: 0.707 AC XY: 270303 AN XY: 382236

African (AFR) AF: 0.714 AC: 12487 AN: 17500

American (AMR) AF: 0.795 AC: 6445 AN: 8110

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 9007 AN: 12614

East Asian (EAS) AF: 0.650 AC: 16425 AN: 25282

South Asian (SAS) AF: 0.830 AC: 11620 AN: 14004

European-Finnish (FIN) AF: 0.763 AC: 16141 AN: 21168

Middle Eastern (MID) AF: 0.785 AC: 1919 AN: 2446

European-Non Finnish (NFE) AF: 0.701 AC: 463267 AN: 660558

Other (OTH) AF: 0.709 AC: 24550 AN: 34602

GnomAD4 genome AF: 0.725 AC: 110274 AN: 152158 Hom.: 40112 Cov.: 33 AF XY: 0.728 AC XY: 54175 AN XY: 74400

African (AFR) AF: 0.712 AC: 29578 AN: 41524

American (AMR) AF: 0.783 AC: 11975 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3059 AN: 5158

South Asian (SAS) AF: 0.827 AC: 3995 AN: 4828

European-Finnish (FIN) AF: 0.772 AC: 8190 AN: 10606

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48676 AN: 67958

Other (OTH) AF: 0.730 AC: 1541 AN: 2112

Alfa AF: 0.730 Hom.: 12680

Bravo AF: 0.720

TwinsUK AF: 0.701 AC: 2599

ALSPAC AF: 0.706 AC: 2721

Asia WGS AF: 0.761 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.59
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0031	T
PhyloP100		0.017
GERP RS		-5.7
PromoterAI		-0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs10891246; hg19: chr11-111170540; COSMIC: COSV62618845; COSMIC: COSV62618845;