Variant 8-90044862-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_001359.2(DECR1):c.752G>A(p.Arg251His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,612,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

DECR1
NM_001359.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.49

Variant links:

Genes affected

DECR1 (HGNC:2753): (2,4-dienoyl-CoA reductase 1) Enables 2,4-dienoyl-CoA reductase (NADPH) activity; NADPH binding activity; and identical protein binding activity. Involved in fatty acid beta-oxidation. Located in cytosol; mitochondrion; and nucleoplasm. Part of catalytic complex. [provided by Alliance of Genome Resources, Apr 2022]

DECR1 links:

DECR1 (HGNC:):

DECR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity DECR_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DECR1	NM_001359.2 linkuse as main transcript	c.752G>A	p.Arg251His	missense_variant	8/10	ENST00000220764.7	NP_001350.1	Q16698-1A0A024R9D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DECR1	ENST00000220764.7 linkuse as main transcript	c.752G>A	p.Arg251His	missense_variant	8/10	1	NM_001359.2	ENSP00000220764.2		Q16698-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250566

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1460516

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000119

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

Sep 27, 2021

The c.752G>A (p.R251H) alteration is located in exon 8 (coding exon 8) of the DECR1 gene. This alteration results from a G to A substitution at nucleotide position 752, causing the arginine (R) at amino acid position 251 to be replaced by a histidine (H). 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

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.98

D;.

Vest4

0.92

MutPred

0.51

Loss of methylation at R251 (P = 0.0211);.;

MVP

0.73

MPC

0.36

ClinPred

0.73

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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