rs371492548

Variant names:

• chr12-6967927-C-T
• rs371492548
• NM_001144831.2:c.572G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6967927-C-T
• chr12-6967927-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001144831.2(PHB2):​c.572G>A​(p.Arg191Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000226 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PHB2 NM_001144831.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2699538).
• BS2: High AC in GnomAd4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144831.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHB2	NM_001144831.2	MANE Select	c.572G>A	p.Arg191Gln	missense	Exon 5 of 10	NP_001138303.1	Q99623-1
	PHB2	NM_001267700.1		c.572G>A	p.Arg191Gln	missense	Exon 5 of 9	NP_001254629.1	Q99623-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHB2	ENST00000535923.6	TSL:5 MANE Select	c.572G>A	p.Arg191Gln	missense	Exon 5 of 10	ENSP00000441875.1	Q99623-1
	PHB2	ENST00000925249.1		c.572G>A	p.Arg191Gln	missense	Exon 5 of 9	ENSP00000595308.1
	PHB2	ENST00000542912.5	TSL:5	c.572G>A	p.Arg191Gln	missense	Exon 5 of 8	ENSP00000440317.1	F5GY37

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000181 AC: 45 AN: 249186 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000233 AC: 341 AN: 1461616 Hom.: 0 Cov.: 32 AF XY: 0.000216 AC XY: 157 AN XY: 727074

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000289 AC: 321 AN: 1111806

Other (OTH) AF: 0.000133 AC: 8 AN: 60372

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000351 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.10
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.1	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.52
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Polyphen		0.59	P
Vest4		0.55
MVP		0.96
MPC		0.95
ClinPred		0.059	T
GERP RS		4.1
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.41
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs371492548; hg19: chr12-7077090;