rs4656538

Variant names:

• chr1-167290518-A-G
• rs4656538
• NM_002697.4:c.62-41952A>G

Variant summary

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

The NM_002697.4(POU2F1):​c.62-41952A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,192 control chromosomes in the GnomAD database, including 14,956 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 0.41 (14956 hom., cov: 33)
• Consequence: POU2F1 NM_002697.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 10 publications found

Genes affected

POU2F1 (HGNC:9212): (POU class 2 homeobox 1) The OCT1 transcription factor was among the first identified members of the POU transcription factor family (summarized by Sturm et al., 1993 [PubMed 8314572]). Members of this family contain the POU domain, a 160-amino acid region necessary for DNA binding to the octameric sequence ATGCAAAT.[supplied by OMIM, Jul 2010]

LOC124900412 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002697.4. 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
	POU2F1	NM_002697.4	MANE Select	c.62-41952A>G		intron	N/A	NP_002688.3
	POU2F1	NM_001365848.1		c.-303-41952A>G		intron	N/A	NP_001352777.1	A0A8A2IE78
	POU2F1	NM_001365849.1		c.-303-41952A>G		intron	N/A	NP_001352778.1	A0A8A2IE78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2F1	ENST00000367866.7	TSL:1 MANE Select	c.62-41952A>G		intron	N/A	ENSP00000356840.2	P14859-6
	POU2F1	ENST00000541643.7	TSL:1	c.-109-12956A>G		intron	N/A	ENSP00000441285.2	P14859-1
	POU2F1	ENST00000271411.8	TSL:1	n.62-12956A>G		intron	N/A	ENSP00000271411.5	Q16075

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61738 AN: 152074 Hom.: 14941 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.406 AC: 61769 AN: 152192 Hom.: 14956 Cov.: 33 AF XY: 0.419 AC XY: 31192 AN XY: 74414

African (AFR) AF: 0.143 AC: 5954 AN: 41540

American (AMR) AF: 0.534 AC: 8152 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.696 AC: 3603 AN: 5176

South Asian (SAS) AF: 0.622 AC: 3002 AN: 4824

European-Finnish (FIN) AF: 0.585 AC: 6203 AN: 10604

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32210 AN: 67986

Other (OTH) AF: 0.413 AC: 874 AN: 2114

Alfa AF: 0.452 Hom.: 53636

Bravo AF: 0.392

Asia WGS AF: 0.642 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-0.25
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: rs4656538; hg19: chr1-167259755;