rs4656538

Positions:

• chr1-167290518-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2F1	NM_002697.4	c.62-41952A>G		intron_variant		ENST00000367866.7	NP_002688.3
LOC124900412	XR_007066718.1	n.46471A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2F1	ENST00000367866.7	c.62-41952A>G		intron_variant		1	NM_002697.4	ENSP00000356840	A1

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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.413

Alfa AF: 0.469 Hom.: 36041

Bravo AF: 0.392

Asia WGS AF: 0.642 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.62

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: rs4656538; hg19: chr1-167259755;