chr12-6966719-C-T

Position:

• chr12-6966719-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144831.2(PHB2):​c.790-219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,102 control chromosomes in the GnomAD database, including 7,427 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 0.23 (7427 hom., cov: 32)
• Consequence: PHB2 NM_001144831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHB2	NM_001144831.2	c.790-219G>A		intron_variant		ENST00000535923.6	NP_001138303.1
PHB2	NM_001267700.1	c.676-219G>A		intron_variant			NP_001254629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHB2	ENST00000535923.6	c.790-219G>A		intron_variant		5	NM_001144831.2	ENSP00000441875.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 151984 Hom.: 7392 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35312 AN: 152102 Hom.: 7427 Cov.: 32 AF XY: 0.227 AC XY: 16848 AN XY: 74380

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0589

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.192

Alfa AF: 0.182 Hom.: 971

Bravo AF: 0.252

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs2110073; hg19: chr12-7075882;