chr17-49404181-G-A

Position:

• chr17-49404181-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PHB1	NM_002634.4	c.*811C>T		3_prime_UTR_variant	7/7	ENST00000300408.8	NP_002625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHB1	ENST00000300408.8	c.*811C>T		3_prime_UTR_variant	7/7	1	NM_002634.4	ENSP00000300408	P1
	ENST00000506504.3	n.101G>A		non_coding_transcript_exon_variant	1/2	3
	ENST00000576461.1	n.270+31095G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24792 AN: 152094 Hom.: 2138 Cov.: 32

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: 87 AN: 504 Hom.: 10 Cov.: 0 AF XY: 0.167 AC XY: 52 AN XY: 312

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.163 AC: 24796 AN: 152212 Hom.: 2136 Cov.: 32 AF XY: 0.164 AC XY: 12196 AN XY: 74402

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.156

Alfa AF: 0.177 Hom.: 2679

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
DANN	Benign	0.75

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: rs6917; hg19: chr17-47481543; COSMIC: COSV55931418; COSMIC: COSV55931418;