rs1805809

Variant names:

• chr8-90010890-T-C
• rs1805809
• NM_001359.2:c.70-6234T>C

Variant summary

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

The NM_001359.2(DECR1):​c.70-6234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,060 control chromosomes in the GnomAD database, including 21,993 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 0.51 (21993 hom., cov: 32)
• Consequence: DECR1 NM_001359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DECR1	NM_001359.2	c.70-6234T>C		intron_variant	Intron 1 of 9	ENST00000220764.7	NP_001350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DECR1	ENST00000220764.7	c.70-6234T>C		intron_variant	Intron 1 of 9	1	NM_001359.2	ENSP00000220764.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77168 AN: 151942 Hom.: 21923 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.508 AC: 77310 AN: 152060 Hom.: 21993 Cov.: 32 AF XY: 0.514 AC XY: 38209 AN XY: 74298

African (AFR) AF: 0.768 AC: 31867 AN: 41480

American (AMR) AF: 0.518 AC: 7920 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1185 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3365 AN: 5180

South Asian (SAS) AF: 0.531 AC: 2562 AN: 4824

European-Finnish (FIN) AF: 0.434 AC: 4565 AN: 10530

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24420 AN: 67986

Other (OTH) AF: 0.493 AC: 1038 AN: 2104

Alfa AF: 0.455 Hom.: 2193

Bravo AF: 0.525

Asia WGS AF: 0.626 AC: 2176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.022
DANN	Benign	0.26
PhyloP100		-3.3
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: rs1805809; hg19: chr8-91023118;