Variant X-85277990-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024921.4(POF1B):c.*1431A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 110,178 control chromosomes in the GnomAD database, including 2,443 homozygotes. There are 6,595 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 2441 hom., 6573 hem., cov: 22)

Exomes 𝑓: 0.17 ( 2 hom. 22 hem. )

Consequence

POF1B
NM_024921.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.783

Variant links:

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]

POF1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-85277990-T-G is Benign according to our data. Variant chrX-85277990-T-G is described in ClinVar as [Benign]. Clinvar id is 368763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POF1B	NM_024921.4 linkuse as main transcript	c.*1431A>C		3_prime_UTR_variant	17/17	ENST00000262753.9	NP_079197.3	Q8WVV4-2
POF1B	XM_005262203.5 linkuse as main transcript	c.*1431A>C		3_prime_UTR_variant	17/17		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753 linkuse as main transcript	c.*1431A>C		3_prime_UTR_variant	17/17	1	NM_024921.4	ENSP00000262753.4		Q8WVV4-2

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

23630

AN:

109829

Hom.:

2443

Cov.:

AF XY:

0.201

AC XY:

6537

AN XY:

32457

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.0411

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.119

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.166

AC:

AN:

302

Hom.:

Cov.:

AF XY:

0.169

AC XY:

AN XY:

130

show subpopulations

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.215

AC:

23670

AN:

109876

Hom.:

2441

Cov.:

AF XY:

0.202

AC XY:

6573

AN XY:

32514

show subpopulations

Gnomad4 AFR

AF:

0.402

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.189

Hom.:

1103

Bravo

AF:

0.219

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 2B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Non-syndromic X-linked intellectual disability

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over