rs10494474

chr1-167229943-C-G

Variant summary

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

The NM_002697.4(POU2F1):c.61+8985C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,152 control chromosomes in the GnomAD database, including 14,673 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 0.40 (14673 hom., cov: 32)
• Consequence: POU2F1 NM_002697.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2F1	NM_002697.4	c.61+8985C>G		intron_variant		ENST00000367866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2F1	ENST00000367866.7	c.61+8985C>G		intron_variant		1	NM_002697.4	A1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60383 AN: 152034 Hom.: 14658 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.397 AC: 60408 AN: 152152 Hom.: 14673 Cov.: 32 AF XY: 0.410 AC XY: 30489 AN XY: 74376

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.407

Alfa AF: 0.430 Hom.: 2119

Bravo AF: 0.382

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.6
Dann	Benign	0.77

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: rs10494474; hg19: chr1-167199180;