Genetic Variant DECR1:p.Pro240Leu (chr8-90042781-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001359.2(DECR1):c.719C>T(p.Pro240Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,424 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

DECR1
NM_001359.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.50

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

liver disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
progressive encephalopathy with leukodystrophy due to DECR deficiency
Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

DECR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0982399).

BP6

Variant 8-90042781-C-T is Benign according to our data. Variant chr8-90042781-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 749396.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001359.2. 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
	DECR1	NM_001359.2	MANE Select	c.719C>T	p.Pro240Leu	missense	Exon 7 of 10	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.692C>T	p.Pro231Leu	missense	Exon 9 of 12	NP_001317504.1	Q16698-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DECR1	ENST00000220764.7	TSL:1 MANE Select	c.719C>T	p.Pro240Leu	missense	Exon 7 of 10	ENSP00000220764.2	Q16698-1
DECR1	ENST00000519328.5	TSL:1	n.*290C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000431045.1	E5RGS6
DECR1	ENST00000519328.5	TSL:1	n.*290C>T		3_prime_UTR	Exon 5 of 8	ENSP00000431045.1	E5RGS6

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152022

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:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000545

AC:

137

AN:

251220

AF XY:

0.000714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000242

AC:

353

AN:

1461284

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39660

South Asian (SAS)

AF:

0.00393

AC:

339

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111598

Other (OTH)

AF:

0.000166

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41514

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00290

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000341

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000577

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Progressive encephalopathy with leukodystrophy due to DECR deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.059

MetaRNN

Benign

0.098

MetaSVM

Uncertain

0.032

MutationAssessor

Pathogenic

3.9

PhyloP100

7.5

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-9.7

REVEL

Uncertain

0.59

Sift

Benign

0.031

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.83

MutPred

0.88

Gain of MoRF binding (P = 0.0416)

MVP

0.76

MPC

0.33

ClinPred

0.51

GERP RS

5.2

Varity_R

0.94

gMVP

0.99

Mutation Taster

=8/92

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over