chr8-90019960-T-G

Variant names:

• chr8-90019960-T-G
• rs1805880
• NM_001359.2:c.417+788T>G

Variant summary

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

The NM_001359.2(DECR1):​c.417+788T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,304 control chromosomes in the GnomAD database, including 284 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 0.043 (284 hom., cov: 32)
• Consequence: DECR1 NM_001359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DECR1	NM_001359.2	MANE Select	c.417+788T>G		intron	N/A	NP_001350.1
	DECR1	NM_001330575.2		c.390+788T>G		intron	N/A	NP_001317504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DECR1	ENST00000220764.7	TSL:1 MANE Select	c.417+788T>G		intron	N/A	ENSP00000220764.2
	DECR1	ENST00000519328.5	TSL:1	n.*88+788T>G		intron	N/A	ENSP00000431045.1
	DECR1	ENST00000522161.5	TSL:2	c.390+788T>G		intron	N/A	ENSP00000429779.1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6517 AN: 152184 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0304

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0428 AC: 6525 AN: 152304 Hom.: 284 Cov.: 32 AF XY: 0.0480 AC XY: 3575 AN XY: 74480

African (AFR) AF: 0.00947 AC: 394 AN: 41588

American (AMR) AF: 0.111 AC: 1695 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5180

South Asian (SAS) AF: 0.0756 AC: 365 AN: 4830

European-Finnish (FIN) AF: 0.0784 AC: 831 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0304 AC: 2069 AN: 68016

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0383 Hom.: 20

Bravo AF: 0.0466

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		1.1
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: rs1805880; hg19: chr8-91032188;