Variant 11-117171707-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001184746.2(PAFAH1B2):c.497C>G(p.Pro166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,535,910 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

PAFAH1B2
NM_001184746.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.284

Variant links:

Genes affected

PAFAH1B2 (HGNC:8575): (platelet activating factor acetylhydrolase 1b catalytic subunit 2) Platelet-activating factor acetylhydrolase (PAFAH) inactivates platelet-activating factor (PAF) into acetate and LYSO-PAF. This gene encodes the beta subunit of PAFAH, the other subunits are alpha and gamma. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2014]

PAFAH1B2 links:

PAFAH1B2 (HGNC:):

PAFAH1B2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037748218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PAFAH1B2	NM_001184746.2 linkuse as main transcript	c.497C>G	p.Pro166Arg	missense_variant	6/7	NP_001171675.1	P68402-4
PAFAH1B2	XM_017017840.2 linkuse as main transcript	c.*4008C>G		3_prime_UTR_variant	6/8	XP_016873329.1
PAFAH1B2	XM_047427042.1 linkuse as main transcript	c.*4008C>G		3_prime_UTR_variant	6/8	XP_047282998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
PAFAH1B2	ENST00000530272.1 linkuse as main transcript	c.497C>G	p.Pro166Arg	missense_variant	6/7	1	ENSP00000431365.1	P68402-4
PAFAH1B2	ENST00000529887.6 linkuse as main transcript	c.412-4199C>G		intron_variant		1	ENSP00000434951.2	P68402-2
PAFAH1B2	ENST00000419197.6 linkuse as main transcript	c.394-3186C>G		intron_variant		2	ENSP00000388742.2	P68402-3
PAFAH1B2	ENST00000526888.1 linkuse as main transcript	n.111-4199C>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000334

AC:

AN:

134570

Hom.:

AF XY:

0.000314

AC XY:

AN XY:

73286

show subpopulations

Gnomad AFR exome

AF:

0.00621

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000135

AC:

187

AN:

1383630

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

682782

show subpopulations

Gnomad4 AFR exome

AF:

0.00522

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152280

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00457

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.00153

ExAC

AF:

0.000238

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.497C>G (p.P166R) alteration is located in exon 6 (coding exon 5) of the PAFAH1B2 gene. This alteration results from a C to G substitution at nucleotide position 497, causing the proline (P) at amino acid position 166 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.2

DANN

Benign

0.96

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.25

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.27

REVEL

Benign

0.063

Sift

Uncertain

0.022

Sift4G

Benign

0.24

Vest4

0.17

MVP

0.14

ClinPred

0.019

GERP RS

0.50

Splicing

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