chr7-38987294-C-A

Variant names:

• chr7-38987294-C-A
• rs859516
• NM_001370959.1:c.105+9236C>A

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+9236C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,992 control chromosomes in the GnomAD database, including 2,728 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 0.18 (2728 hom., cov: 32)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 3 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=-0.83).
• 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 rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.105+9236C>A		intron_variant	Intron 1 of 9	ENST00000518318.7	NP_001357888.1
POU6F2	NM_007252.4	c.-94+9236C>A		intron_variant	Intron 1 of 10		NP_009183.3
POU6F2	NM_001166018.2	c.-94+9236C>A		intron_variant	Intron 1 of 10		NP_001159490.1
POU6F2-AS2	NR_138047.1	n.523+1341G>T		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.105+9236C>A		intron_variant	Intron 1 of 9	1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27356 AN: 151874 Hom.: 2723 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.180 AC: 27362 AN: 151992 Hom.: 2728 Cov.: 32 AF XY: 0.174 AC XY: 12952 AN XY: 74294

African (AFR) AF: 0.126 AC: 5240 AN: 41482

American (AMR) AF: 0.158 AC: 2410 AN: 15264

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

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5172

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4816

European-Finnish (FIN) AF: 0.197 AC: 2077 AN: 10570

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

European-Non Finnish (NFE) AF: 0.227 AC: 15442 AN: 67912

Other (OTH) AF: 0.215 AC: 453 AN: 2104

Alfa AF: 0.178 Hom.: 1070

Bravo AF: 0.176

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		0.19
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: rs859516; hg19: chr7-39026894;