rs16980189

Variant names:

• chrX-85277990-T-G
• rs16980189
• NM_024921.4:c.*1431A>C

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.783
• Publications: 1 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=-0.92).
• 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 rank	MANE	Protein	UniProt
POF1B	NM_024921.4	c.*1431A>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000262753.9	NP_079197.3
POF1B	XM_005262203.5	c.*1431A>C		3_prime_UTR_variant	Exon 17 of 17		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753.9	c.*1431A>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_024921.4	ENSP00000262753.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 23630 AN: 109829 Hom.: 2443 Cov.: 22

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: 50 AN: 302 Hom.: 2 Cov.: 0 AF XY: 0.169 AC XY: 22 AN XY: 130

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) AF: 0.164 AC: 49 AN: 298

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1

Other (OTH) AF: 0.333 AC: 1 AN: 3

GnomAD4 genome AF: 0.215 AC: 23670 AN: 109876 Hom.: 2441 Cov.: 22 AF XY: 0.202 AC XY: 6573 AN XY: 32514

African (AFR) AF: 0.402 AC: 12151 AN: 30222

American (AMR) AF: 0.152 AC: 1564 AN: 10268

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 470 AN: 2617

East Asian (EAS) AF: 0.151 AC: 527 AN: 3499

South Asian (SAS) AF: 0.194 AC: 515 AN: 2648

European-Finnish (FIN) AF: 0.156 AC: 912 AN: 5834

Middle Eastern (MID) AF: 0.131 AC: 28 AN: 214

European-Non Finnish (NFE) AF: 0.137 AC: 7201 AN: 52396

Other (OTH) AF: 0.183 AC: 274 AN: 1496

Alfa AF: 0.189 Hom.: 1103

Bravo AF: 0.219

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Premature ovarian failure 2B Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Non-syndromic X-linked intellectual disability Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.78
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: rs16980189; hg19: chrX-84532996; COSMIC: COSV53138282; COSMIC: COSV53138282;