Variant 12-6965713-CTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001144831.2(PHB2):c.873-3_873-2delCA variant causes a splice acceptor, splice region, intron change. The variant allele was found at a frequency of 0.00153 in 1,611,168 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 74 hom. )

Consequence

PHB2
NM_001144831.2 splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

PHB2 (HGNC:30306): (prohibitin 2) Enables several functions, including protein C-terminus binding activity; protein N-terminus binding activity; and protein dimerization activity. Involved in several processes, including defense response to virus; positive regulation of cell cycle phase transition; and regulation of transcription, DNA-templated. Located in several cellular components, including cell surface; mitochondrial membrane; and nuclear matrix. Part of mitochondrial prohibitin complex. [provided by Alliance of Genome Resources, Apr 2022]

PHB2 links:

PHB2 (HGNC:):

PHB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-6965713-CTG-C is Benign according to our data. Variant chr12-6965713-CTG-C is described in ClinVar as [Benign]. Clinvar id is 725611.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00141 (2055/1459290) while in subpopulation EAS AF= 0.0398 (1579/39682). AF 95% confidence interval is 0.0382. There are 74 homozygotes in gnomad4_exome. There are 980 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 411 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHB2	NM_001144831.2 linkuse as main transcript	c.873-3_873-2delCA		splice_acceptor_variant, splice_region_variant, intron_variant		ENST00000535923.6	NP_001138303.1	Q99623-1
PHB2	NM_001267700.1 linkuse as main transcript	c.759-3_759-2delCA		splice_acceptor_variant, splice_region_variant, intron_variant			NP_001254629.1	Q99623-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHB2	ENST00000535923.6 linkuse as main transcript	c.873-3_873-2delCA		splice_acceptor_variant, splice_region_variant, intron_variant		5	NM_001144831.2	ENSP00000441875.1		Q99623-1

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

409

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00788

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0124

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000718

AC:

176

AN:

245120

Hom.:

AF XY:

0.000563

AC XY:

AN XY:

133260

show subpopulations

Gnomad AFR exome

AF:

0.00633

Gnomad AMR exome

AF:

0.000641

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00235

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000729

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.00141

AC:

2055

AN:

1459290

Hom.:

AF XY:

0.00135

AC XY:

980

AN XY:

726016

show subpopulations

Gnomad4 AFR exome

AF:

0.00906

Gnomad4 AMR exome

AF:

0.000807

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0398

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00271

AC:

411

AN:

151878

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

213

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.00790

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0124

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000351

Hom.:

Bravo

AF:

0.00258

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.31

Position offset: -7

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