rs12557215

chrX-85327785-T-CchrX-85327785-T-G

Variant summary

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

The NM_024921.4(POF1B):c.854+3164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 111,501 control chromosomes in the GnomAD database, including 2,487 homozygotes. There are 6,864 hemizygotes in GnomAD. 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 0.22 (2487 hom., 6864 hem., cov: 23)
• Consequence: POF1B NM_024921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

POF1B (HGNC:13711): (POF1B actin binding protein) Premature ovarian failure (POF) is characterized by primary or secondary amenorrhea in women less than 40 years old. Two POF susceptibility regions called "POF1" and "POF2" have been identified by breakpoint mapping of X-autosome translocations. POF1 extends from Xq21-qter while POF2 extends from Xq13.3 to Xq21.1. This gene, POF1B, resides in the POF2 region. This gene is expressed at trace levels in mouse prenatal ovary and is barely detectable or absent from adult ovary, in human and in the mouse respectively. This gene's expression is restricted to epithelia with its highest expression in the epidermis, and oro-pharyngeal and gastro-intestinal tracts. The protein encoded by this gene binds non-muscle actin filaments. The role this gene may play in the etiology of premature ovarian failure remains to be determined. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POF1B	NM_024921.4	c.854+3164A>G		intron_variant		ENST00000262753.9
POF1B	NM_001307940.2	c.854+3164A>G		intron_variant
POF1B	XM_005262203.5	c.809+3164A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POF1B	ENST00000262753.9	c.854+3164A>G		intron_variant		1	NM_024921.4	A2
POF1B	ENST00000373145.3	c.854+3164A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 24112 AN: 111444 Hom.: 2489 Cov.: 23 AF XY: 0.203 AC XY: 6820 AN XY: 33678

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.0423

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.217 AC: 24160 AN: 111501 Hom.: 2487 Cov.: 23 AF XY: 0.203 AC XY: 6864 AN XY: 33745

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.188

Alfa AF: 0.132 Hom.: 2283

Bravo AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.16
Dann	Benign	0.43

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: rs12557215; hg19: chrX-84582791;