rs60464047

Variant names:

• chr7-39378939-T-A
• rs60464047
• NM_001370959.1:c.973-27661T>A

Variant summary

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

The NM_001370959.1(POU6F2):​c.973-27661T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,182 control chromosomes in the GnomAD database, including 1,447 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 0.13 (1447 hom., cov: 32)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

Genes affected

POU6F2 (HGNC:21694): (POU class 6 homeobox 2) This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.973-27661T>A		intron_variant	Intron 5 of 9	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.973-27661T>A		intron_variant	Intron 5 of 9	1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19862 AN: 152064 Hom.: 1447 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.131 AC: 19865 AN: 152182 Hom.: 1447 Cov.: 32 AF XY: 0.132 AC XY: 9834 AN XY: 74414

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.144

Alfa AF: 0.138 Hom.: 194

Bravo AF: 0.135

Asia WGS AF: 0.0850 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.3
DANN	Benign	0.85

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: rs60464047; hg19: chr7-39418538;