rs10494474

Variant names:

• chr1-167229943-C-G
• rs10494474
• NM_002697.4:c.61+8985C>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.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
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2F1	NM_002697.4	MANE Select	c.61+8985C>G		intron	N/A	NP_002688.3
	POU2F1	NM_001365848.1		c.-508+8985C>G		intron	N/A	NP_001352777.1
	POU2F1	NM_001365849.1		c.-304+8985C>G		intron	N/A	NP_001352778.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2F1	ENST00000367866.7	TSL:1 MANE Select	c.61+8985C>G		intron	N/A	ENSP00000356840.2
	POU2F1	ENST00000541643.7	TSL:1	c.-110+8985C>G		intron	N/A	ENSP00000441285.2
	POU2F1	ENST00000271411.8	TSL:1	n.61+8985C>G		intron	N/A	ENSP00000271411.5

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

African (AFR) AF: 0.118 AC: 4890 AN: 41528

American (AMR) AF: 0.524 AC: 8008 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3594 AN: 5170

South Asian (SAS) AF: 0.611 AC: 2947 AN: 4826

European-Finnish (FIN) AF: 0.585 AC: 6190 AN: 10576

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32150 AN: 67978

Other (OTH) AF: 0.407 AC: 858 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		0.45
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: rs10494474; hg19: chr1-167199180;