7-38987345-T-C

Position:

• chr7-38987345-T-C

Variant summary

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

The NM_001370959.1(POU6F2):​c.105+9287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,098 control chromosomes in the GnomAD database, including 2,853 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 0.19 (2853 hom., cov: 32)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

POU6F2-AS2 (HGNC:21887): (POU6F2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.105+9287T>C		intron_variant		ENST00000518318.7	NP_001357888.1
POU6F2	NM_007252.4	c.-94+9287T>C		intron_variant			NP_009183.3
POU6F2	NM_001166018.2	c.-94+9287T>C		intron_variant			NP_001159490.1
POU6F2-AS2	NR_138047.1	n.523+1290A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.105+9287T>C		intron_variant		1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28321 AN: 151980 Hom.: 2847 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.186 AC: 28329 AN: 152098 Hom.: 2853 Cov.: 32 AF XY: 0.180 AC XY: 13403 AN XY: 74366

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.222

Alfa AF: 0.196 Hom.: 1895

Bravo AF: 0.184

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs859515; hg19: chr7-39026945;