NM_001359.2:c.77G>A

Variant names:

• chr8-90017131-G-A
• rs145323335
• NM_001359.2:c.77G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001359.2(DECR1):​c.77G>A​(p.Ser26Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,611,594 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S26I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (11 hom.)
• Consequence: DECR1 NM_001359.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.49
• Publications: 5 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.

• BP6: Variant 8-90017131-G-A is Benign according to our data. Variant chr8-90017131-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 534666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 Unknown,AR gene

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.77G>A	p.Ser26Asn	missense	Exon 2 of 10	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.50G>A	p.Ser17Asn	missense	Exon 4 of 12	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.77G>A	p.Ser26Asn	missense	Exon 2 of 10	ENSP00000220764.2	Q16698-1
	DECR1	ENST00000519328.5	TSL:1	n.70-1778G>A		intron	N/A	ENSP00000431045.1	E5RGS6
	DECR1	ENST00000886497.1		c.77G>A	p.Ser26Asn	missense	Exon 2 of 11	ENSP00000556556.1

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152142 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00221 AC: 552 AN: 249550 AF XY: 0.00221

Gnomad AFR exome AF: 0.000440

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00847

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00315

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00342 AC: 4985 AN: 1459334 Hom.: 11 Cov.: 30 AF XY: 0.00328 AC XY: 2384 AN XY: 725982

African (AFR) AF: 0.000810 AC: 27 AN: 33350

American (AMR) AF: 0.00157 AC: 70 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.00931 AC: 243 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85798

European-Finnish (FIN) AF: 0.00161 AC: 86 AN: 53380

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5720

European-Non Finnish (NFE) AF: 0.00391 AC: 4346 AN: 1110544

Other (OTH) AF: 0.00342 AC: 206 AN: 60290

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152260 Hom.: 1 Cov.: 33 AF XY: 0.00201 AC XY: 150 AN XY: 74446

African (AFR) AF: 0.000794 AC: 33 AN: 41558

American (AMR) AF: 0.00261 AC: 40 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00301 AC: 205 AN: 67996

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00230

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00210 AC: 255

EpiCase AF: 0.00240

EpiControl AF: 0.00314

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DECR1-related disorder (1)
-	-	1	not provided (1)
-	-	1	Progressive encephalopathy with leukodystrophy due to DECR deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.0076	T
MetaSVM	Uncertain	-0.059	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.017	D
Sift4G	Benign	0.24	T
Polyphen		0.36	B
Vest4		0.21
MVP		0.89
MPC		0.047
ClinPred		0.014	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.83
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.46		Position offset: -7

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

Other links and lift over

dbSNP: rs145323335; hg19: chr8-91029359; COSMIC: COSV55168168; COSMIC: COSV55168168;