Variant 5-177992290-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006261.5(PROP1):c.*419C>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 0.0268 in 179,120 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 154 hom., cov: 29)

Exomes 𝑓: 0.018 ( 19 hom. )

Consequence

PROP1
NM_006261.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0760

Variant links:

Genes affected

PROP1 (HGNC:9455): (PROP paired-like homeobox 1) This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domain transcription factor 1, which is responsible for pituitary development and hormone expression. Mutations in this gene have been associated with combined pituitary hormone deficiency-2 as well as deficiencies in luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, and thyroid-stimulating hormone. [provided by RefSeq, Sep 2011]

PROP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 5-177992290-G-A is Benign according to our data. Variant chr5-177992290-G-A is described in ClinVar as [Benign]. Clinvar id is 353008.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROP1	NM_006261.5 linkuse as main transcript	c.*419C>T		3_prime_UTR_variant	3/3	ENST00000308304.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROP1	ENST00000308304.2 linkuse as main transcript	c.*419C>T		3_prime_UTR_variant	3/3	1	NM_006261.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4297

AN:

151528

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00868

Gnomad AMI

AF:

0.00662

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0323

GnomAD4 exome

AF:

0.0183

AC:

502

AN:

27480

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

255

AN XY:

14016

show subpopulations

Gnomad4 AFR exome

AF:

0.00207

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0759

Gnomad4 SAS exome

AF:

0.0954

Gnomad4 FIN exome

AF:

0.00427

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0284

AC:

4299

AN:

151640

Hom.:

154

Cov.:

AF XY:

0.0310

AC XY:

2299

AN XY:

74090

show subpopulations

Gnomad4 AFR

AF:

0.00863

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.0264

Gnomad4 OTH

AF:

0.0319

Alfa

AF:

0.0234

Hom.:

Bravo

AF:

0.0247

Asia WGS

AF:

0.128

AC:

445

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pituitary hormone deficiency, combined, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.9

DANN

Benign

0.23

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