7-38987345-T-C

Variant names:

• chr7-38987345-T-C
• rs859515
• NM_001370959.1:c.105+9287T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	NM_001370959.1	MANE Select	c.105+9287T>C		intron	N/A	NP_001357888.1
	POU6F2	NM_007252.4		c.-94+9287T>C		intron	N/A	NP_009183.3
	POU6F2	NM_001166018.2		c.-94+9287T>C		intron	N/A	NP_001159490.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.105+9287T>C		intron	N/A	ENSP00000430514.3
	POU6F2	ENST00000403058.6	TSL:5	c.-94+9287T>C		intron	N/A	ENSP00000384004.1
	POU6F2-AS2	ENST00000420243.2	TSL:5	n.307-2424A>G		intron	N/A

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

African (AFR) AF: 0.149 AC: 6168 AN: 41500

American (AMR) AF: 0.160 AC: 2437 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.0992 AC: 479 AN: 4828

European-Finnish (FIN) AF: 0.196 AC: 2076 AN: 10578

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15437 AN: 67950

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.198 Hom.: 2117

Bravo AF: 0.184

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs859515; hg19: chr7-39026945;