Variant 17-49409322-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002634.4(PHB1):c.393+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,613,866 control chromosomes in the GnomAD database, including 6,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 2715 hom., cov: 32)

Exomes 𝑓: 0.025 ( 4187 hom. )

Consequence

PHB1
NM_002634.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

PHB1 (HGNC:8912): (prohibitin 1) This gene is evolutionarily conserved, and its product is proposed to play a role in human cellular senescence and tumor suppression. Antiproliferative activity is reported to be localized to the 3' UTR, which is proposed to function as a trans-acting regulatory RNA. Several pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PHB1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-49409322-T-C is Benign according to our data. Variant chr17-49409322-T-C is described in ClinVar as [Benign]. Clinvar id is 3059217.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHB1	NM_002634.4 linkuse as main transcript	c.393+9A>G		intron_variant		ENST00000300408.8	NP_002625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHB1	ENST00000300408.8 linkuse as main transcript	c.393+9A>G		intron_variant		1	NM_002634.4	ENSP00000300408	P1	P35232-1
	ENST00000576461.1 linkuse as main transcript	n.270+36236T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17731

AN:

152018

Hom.:

2700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.0777

GnomAD3 exomes

AF:

0.0655

AC:

16448

AN:

251208

Hom.:

1865

AF XY:

0.0520

AC XY:

7066

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.0223

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.0468

GnomAD4 exome

AF:

0.0249

AC:

36341

AN:

1461730

Hom.:

4187

Cov.:

AF XY:

0.0229

AC XY:

16665

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.0374

GnomAD4 genome

AF:

0.117

AC:

17793

AN:

152136

Hom.:

2715

Cov.:

AF XY:

0.118

AC XY:

8750

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0232

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.00376

Gnomad4 OTH

AF:

0.0769

Alfa

AF:

0.0305

Hom.:

1034

Bravo

AF:

0.137

Asia WGS

AF:

0.0790

AC:

275

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00539

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PHB1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.021

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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