Variant 17-49406866-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002634.4(PHB1):c.511-12C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,594,394 control chromosomes in the GnomAD database, including 76,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5297 hom., cov: 33)

Exomes 𝑓: 0.30 ( 71150 hom. )

Consequence

PHB1
NM_002634.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.004257

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0860

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 17-49406866-G-C is Benign according to our data. Variant chr17-49406866-G-C is described in ClinVar as [Benign]. Clinvar id is 1254039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 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.511-12C>G		splice_polypyrimidine_tract_variant, 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.511-12C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002634.4	ENSP00000300408	P1	P35232-1
	ENST00000576461.1 linkuse as main transcript	n.270+33780G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35624

AN:

152078

Hom.:

5294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.252

AC:

62986

AN:

250298

Hom.:

9338

AF XY:

0.256

AC XY:

34617

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.304

AC:

438045

AN:

1442198

Hom.:

71150

Cov.:

AF XY:

0.300

AC XY:

215450

AN XY:

718890

show subpopulations

Gnomad4 AFR exome

AF:

0.0490

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.234

AC:

35620

AN:

152196

Hom.:

5297

Cov.:

AF XY:

0.234

AC XY:

17388

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.264

Hom.:

1073

Bravo

AF:

0.214

Asia WGS

AF:

0.140

AC:

489

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0043

dbscSNV1_RF

Benign

0.10

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