X-85279053-C-A

Position:

• chrX-85279053-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024921.4(POF1B):​c.*368G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 144,794 control chromosomes in the GnomAD database, including 629 homozygotes. There are 2,361 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (454 hom., 2071 hem., cov: 22)
  • Exomes 𝑓: 0.050 (175 hom. 290 hem.)
• Consequence: POF1B NM_024921.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.296

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-85279053-C-A is Benign according to our data. Variant chrX-85279053-C-A is described in ClinVar as [Benign]. Clinvar id is 368774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POF1B	NM_024921.4	c.*368G>T		3_prime_UTR_variant	17/17	ENST00000262753.9	NP_079197.3
POF1B	XM_005262203.5	c.*368G>T		3_prime_UTR_variant	17/17		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753	c.*368G>T		3_prime_UTR_variant	17/17	1	NM_024921.4	ENSP00000262753.4

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 7196 AN: 110378 Hom.: 458 Cov.: 22 AF XY: 0.0629 AC XY: 2069 AN XY: 32900

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.00333

Gnomad MID AF: 0.0297

Gnomad NFE AF: 0.00430

Gnomad OTH AF: 0.0675

GnomAD4 exome AF: 0.0504 AC: 1732 AN: 34369 Hom.: 175 Cov.: 0 AF XY: 0.0498 AC XY: 290 AN XY: 5821

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.0445

Gnomad4 FIN exome AF: 0.00452

Gnomad4 NFE exome AF: 0.00579

Gnomad4 OTH exome AF: 0.0522

GnomAD4 genome AF: 0.0652 AC: 7204 AN: 110425 Hom.: 454 Cov.: 22 AF XY: 0.0628 AC XY: 2071 AN XY: 32957

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.00333

Gnomad4 NFE AF: 0.00430

Gnomad4 OTH AF: 0.0726

Alfa AF: 0.0208 Hom.: 1078

Bravo AF: 0.0839

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Premature ovarian failure 2B Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.58

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: rs6617041; hg19: chrX-84534059;