rs3767434

Positions:

• chr1-167401914-T-C

Variant summary

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

The NM_002697.4(POU2F1):​c.1555+358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,284 control chromosomes in the GnomAD database, including 1,901 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 0.14 (1901 hom., cov: 32)
• Consequence: POU2F1 NM_002697.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2F1	NM_002697.4	c.1555+358T>C		intron_variant		ENST00000367866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2F1	ENST00000367866.7	c.1555+358T>C		intron_variant		1	NM_002697.4	A1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21865 AN: 152166 Hom.: 1902 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.144 AC: 21857 AN: 152284 Hom.: 1901 Cov.: 32 AF XY: 0.140 AC XY: 10436 AN XY: 74460

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.157

Alfa AF: 0.171 Hom.: 677

Bravo AF: 0.138

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.50

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: rs3767434; hg19: chr1-167371151;