dbSNP rs6917: PHB1:c.*811C>T (chr17-49404181-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002634.4(PHB1):c.*811C>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 0.163 in 152,716 control chromosomes in the GnomAD database, including 2,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2136 hom., cov: 32)

Exomes 𝑓: 0.17 ( 10 hom. )

Consequence

PHB1
NM_002634.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.100

Publications

41 publications found

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:

ENSG00000250186 (HGNC:):

ENSG00000250186 links:

ZNF652-AS1 (HGNC:55582): (ZNF652 antisense RNA 1)

ZNF652-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHB1	NM_002634.4 link	c.*811C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000300408.8	NP_002625.1	P35232-1A8K401Q53FV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHB1	ENST00000300408.8 link	c.*811C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_002634.4	ENSP00000300408.3		P35232-1
PHB1	ENST00000511832.6 link	c.*811C>T		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000425035.2		P35232-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24792

AN:

152094

Hom.:

2138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.173

AC:

AN:

504

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.171

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.286

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24796

AN:

152212

Hom.:

2136

Cov.:

AF XY:

0.164

AC XY:

12196

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.127

AC:

5283

AN:

41552

American (AMR)

AF:

0.135

AC:

2061

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

771

AN:

5176

South Asian (SAS)

AF:

0.226

AC:

1086

AN:

4810

European-Finnish (FIN)

AF:

0.191

AC:

2024

AN:

10586

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12413

AN:

68006

Other (OTH)

AF:

0.156

AC:

330

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1074

2148

3222

4296

5370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.171

Hom.:

3699

Bravo

AF:

0.155

Asia WGS

AF:

0.156

AC:

540

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

(source)

DANN

Benign

0.75

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over