X-85277572-C-T

Variant names:

• chrX-85277572-C-T
• rs73513629
• NM_024921.4:c.*1849G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024921.4(POF1B):​c.*1849G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 110,074 control chromosomes in the GnomAD database, including 828 homozygotes. There are 2,442 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (828 hom., 2442 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: POF1B NM_024921.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.638
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant X-85277572-C-T is Benign according to our data. Variant chrX-85277572-C-T is described in ClinVar as Benign. ClinVar VariationId is 368759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024921.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POF1B	NM_024921.4	MANE Select	c.*1849G>A		3_prime_UTR	Exon 17 of 17	NP_079197.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POF1B	ENST00000262753.9	TSL:1 MANE Select	c.*1849G>A		3_prime_UTR	Exon 17 of 17	ENSP00000262753.4	Q8WVV4-2
	POF1B	ENST00000871676.1		c.*1849G>A		3_prime_UTR	Exon 18 of 18	ENSP00000541735.1
	POF1B	ENST00000871681.1		c.*1849G>A		3_prime_UTR	Exon 16 of 16	ENSP00000541740.1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 8990 AN: 110027 Hom.: 828 Cov.: 22

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.000762

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00252

Gnomad MID AF: 0.0216

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0693

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0819 AC: 9012 AN: 110074 Hom.: 828 Cov.: 22 AF XY: 0.0749 AC XY: 2442 AN XY: 32610

African (AFR) AF: 0.266 AC: 8045 AN: 30254

American (AMR) AF: 0.0617 AC: 636 AN: 10303

Ashkenazi Jewish (ASJ) AF: 0.000762 AC: 2 AN: 2626

East Asian (EAS) AF: 0.0216 AC: 75 AN: 3465

South Asian (SAS) AF: 0.0238 AC: 63 AN: 2644

European-Finnish (FIN) AF: 0.00252 AC: 15 AN: 5962

Middle Eastern (MID) AF: 0.0237 AC: 5 AN: 211

European-Non Finnish (NFE) AF: 0.00132 AC: 69 AN: 52437

Other (OTH) AF: 0.0685 AC: 102 AN: 1490

Alfa AF: 0.0503 Hom.: 256

Bravo AF: 0.0941

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Non-syndromic X-linked intellectual disability (1)
-	-	1	not provided (1)
-	-	1	Premature ovarian failure 2B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.57
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73513629; hg19: chrX-84532578;