Variant 2-216058896-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018441.6(PECR):c.505G>C(p.Val169Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,565,178 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

PECR
NM_018441.6 missense, splice_region

Scores

Splicing: ADA: 0.0001241

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0690

Variant links:

Genes affected

PECR (HGNC:18281): (peroxisomal trans-2-enoyl-CoA reductase) Enables signaling receptor binding activity and trans-2-enoyl-CoA reductase (NADPH) activity. Involved in phytol metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

PECR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007910341).

BP6

Variant 2-216058896-C-G is Benign according to our data. Variant chr2-216058896-C-G is described in ClinVar as [Benign]. Clinvar id is 790515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (804/152288) while in subpopulation AFR AF= 0.0185 (767/41544). AF 95% confidence interval is 0.0174. There are 13 homozygotes in gnomad4. There are 374 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PECR	NM_018441.6 linkuse as main transcript	c.505G>C	p.Val169Leu	missense_variant, splice_region_variant	4/8	ENST00000265322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PECR	ENST00000265322.8 linkuse as main transcript	c.505G>C	p.Val169Leu	missense_variant, splice_region_variant	4/8	1	NM_018441.6	P1	Q9BY49-1
PECR	ENST00000461330.5 linkuse as main transcript	n.386G>C		splice_region_variant, non_coding_transcript_exon_variant	3/7	2
PECR	ENST00000497889.5 linkuse as main transcript	n.509G>C		splice_region_variant, non_coding_transcript_exon_variant	4/7	5
PECR	ENST00000442122.5 linkuse as main transcript	c.424+6416G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

804

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00129

AC:

323

AN:

251232

Hom.:

AF XY:

0.000884

AC XY:

120

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.000897

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:

0.0000176

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000486

AC:

687

AN:

1412890

Hom.:

Cov.:

AF XY:

0.000415

AC XY:

293

AN XY:

706118

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00528

AC:

804

AN:

152288

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

374

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.00592

ESP6500AA

AF:

0.0175

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00161

AC:

195

Asia WGS

AF:

0.000577

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

Jan 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.7

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.77

REVEL

Benign

0.064

Sift

Uncertain

0.029

Sift4G

Uncertain

0.047

Polyphen

0.0

Vest4

0.12

MutPred

0.67

Loss of MoRF binding (P = 0.3539);

MVP

0.19

MPC

0.051

ClinPred

0.0057

GERP RS

0.058

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.056

SpliceAI score (max)

0.11

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

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