8-90016131-G-A

Variant names:

• chr8-90016131-G-A
• rs2158423
• NM_001359.2:c.70-993G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001359.2(DECR1):​c.70-993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,022 control chromosomes in the GnomAD database, including 6,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (6533 hom., cov: 32)
• Consequence: DECR1 NM_001359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

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.70-993G>A		intron	N/A	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.43-993G>A		intron	N/A	NP_001317504.1	Q16698-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DECR1	ENST00000220764.7	TSL:1 MANE Select	c.70-993G>A		intron	N/A	ENSP00000220764.2	Q16698-1
	DECR1	ENST00000519328.5	TSL:1	n.70-2778G>A		intron	N/A	ENSP00000431045.1	E5RGS6
	DECR1	ENST00000886497.1		c.70-993G>A		intron	N/A	ENSP00000556556.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33136 AN: 151904 Hom.: 6489 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33256 AN: 152022 Hom.: 6533 Cov.: 32 AF XY: 0.220 AC XY: 16370 AN XY: 74306

African (AFR) AF: 0.518 AC: 21463 AN: 41422

American (AMR) AF: 0.223 AC: 3412 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 265 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1342 AN: 5186

South Asian (SAS) AF: 0.185 AC: 889 AN: 4816

European-Finnish (FIN) AF: 0.0911 AC: 962 AN: 10560

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4410 AN: 67978

Other (OTH) AF: 0.208 AC: 439 AN: 2114

Alfa AF: 0.102 Hom.: 326

Bravo AF: 0.243

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2158423; hg19: chr8-91028359;