Genetic Variant NM_024921.4:c.854+3164A>G (chrX-85327785-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

premature ovarian failure 2B
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

POF1B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
POF1B	NM_024921.4 link	c.854+3164A>G	intron_variant	Intron 7 of 16	ENST00000262753.9	NP_079197.3	Q8WVV4-2
POF1B	NM_001307940.2 link	c.854+3164A>G	intron_variant	Intron 7 of 15		NP_001294869.1	Q8WVV4-1
POF1B	XM_005262203.5 link	c.809+3164A>G	intron_variant	Intron 7 of 16		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753.9 link	c.854+3164A>G		intron_variant	Intron 7 of 16	1	NM_024921.4	ENSP00000262753.4		Q8WVV4-2
POF1B	ENST00000373145.3 link	c.854+3164A>G		intron_variant	Intron 7 of 15	1		ENSP00000362238.3		Q8WVV4-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

24112

AN:

111444

Hom.:

2489

Cov.:

show subpopulations

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.:

AF XY:

0.203

AC XY:

6864

AN XY:

33745

show subpopulations

African (AFR)

AF:

0.405

AC:

12383

AN:

30570

American (AMR)

AF:

0.156

AC:

1639

AN:

10520

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

472

AN:

2645

East Asian (EAS)

AF:

0.150

AC:

533

AN:

3543

South Asian (SAS)

AF:

0.197

AC:

529

AN:

2681

European-Finnish (FIN)

AF:

0.156

AC:

939

AN:

6003

Middle Eastern (MID)

AF:

0.123

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.138

AC:

7324

AN:

53123

Other (OTH)

AF:

0.188

AC:

286

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

626

1252

1877

2503

3129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.155

Hom.:

4304

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

(source)

DANN

Benign

0.43

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over