dbSNP rs974678800: DECR1:c.69+4684C>T (chr8-90006245-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_001330575.2(DECR1):c.10C>T(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000426 in 703,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

DECR1
NM_001330575.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.511

Publications

0 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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-90006245-C-T is Benign according to our data. Variant chr8-90006245-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3352711.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.511 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330575.2. 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.69+4684C>T		intron	N/A	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.10C>T	p.Leu4Leu	synonymous	Exon 3 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.69+4684C>T		intron	N/A	ENSP00000220764.2	Q16698-1
DECR1	ENST00000519328.5	TSL:1	n.69+4684C>T		intron	N/A	ENSP00000431045.1	E5RGS6
DECR1	ENST00000522161.5	TSL:2	c.10C>T	p.Leu4Leu	synonymous	Exon 3 of 12	ENSP00000429779.1	Q16698-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000362

AC:

AN:

551802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

298672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15808

American (AMR)

AF:

0.00

AC:

AN:

34708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20028

East Asian (EAS)

AF:

0.00

AC:

AN:

32104

South Asian (SAS)

AF:

0.00

AC:

AN:

62772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

316964

Other (OTH)

AF:

0.00

AC:

AN:

30618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DECR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

(source)

DANN

Benign

0.73

PhyloP100

-0.51

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over