2-104887864-A-G

Variant names:

• chr2-104887864-A-G
• rs1026220
• ENST00000733507.1:n.1270T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000733507.1(ENSG00000295887):​n.1270T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,052 control chromosomes in the GnomAD database, including 28,816 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 0.61 (28816 hom., cov: 33)
• Consequence: ENSG00000295887 ENST00000733507.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637
• Publications: 6 publications found

Genes affected

ENSG00000295887 (HGNC:):

POU3F3 (HGNC:9216): (POU class 3 homeobox 3) This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

POU3F3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• snijders blok-fisher syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000733507.1. 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
	POU3F3	NR_197431.1		n.294+34295A>G		intron	N/A
	POU3F3	NR_197432.1		n.295-11884A>G		intron	N/A
	POU3F3	NR_197433.1		n.354+34032A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295887	ENST00000733507.1		n.1270T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000295887	ENST00000733508.1		n.895T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000295887	ENST00000733509.1		n.813T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93060 AN: 151934 Hom.: 28808 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.612 AC: 93111 AN: 152052 Hom.: 28816 Cov.: 33 AF XY: 0.614 AC XY: 45611 AN XY: 74324

African (AFR) AF: 0.607 AC: 25158 AN: 41462

American (AMR) AF: 0.633 AC: 9673 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2015 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4511 AN: 5178

South Asian (SAS) AF: 0.493 AC: 2375 AN: 4820

European-Finnish (FIN) AF: 0.622 AC: 6573 AN: 10560

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40824 AN: 67960

Other (OTH) AF: 0.633 AC: 1337 AN: 2112

Alfa AF: 0.606 Hom.: 47267

Bravo AF: 0.619

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1026220; hg19: chr2-105504322;