11-111299815-A-G

Position:

• chr11-111299815-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000610738.6(POU2AF3):​c.8-712A>G variant causes a intron 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. 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 ENST00000610738.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.8-712A>G		intron_variant		ENST00000610738.6	NP_001258387.1
COLCA1	NR_169237.1	n.222-1149T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6	c.8-712A>G		intron_variant		1	NM_001271458.2	ENSP00000484135	P2
COLCA1	ENST00000620864.1	n.219-1149T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.714

Gnomad4 EAS exome AF: 0.650

Gnomad4 SAS exome AF: 0.830

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.709

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

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.730

Alfa AF: 0.734 Hom.: 7402

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P;P;P
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10891246; hg19: chr11-111170540; COSMIC: COSV62618845; COSMIC: COSV62618845;