chr2-210210185-T-C

Variant names:

• chr2-210210185-T-C
• rs3764913
• NM_001608.4:c.603+11A>G

Variant summary

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

The NM_001608.4(ACADL):​c.603+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,602,180 control chromosomes in the GnomAD database, including 90,828 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 0.27 (6401 hom., cov: 32)
  • Exomes 𝑓: 0.34 (84427 hom.)
• Consequence: ACADL NM_001608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 28 publications found

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

ACADL Gene-Disease associations (from GenCC):

• long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001608.4. 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
	ACADL	NM_001608.4	MANE Select	c.603+11A>G		intron	N/A	NP_001599.1	P28330

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADL	ENST00000233710.4	TSL:1 MANE Select	c.603+11A>G		intron	N/A	ENSP00000233710.3	P28330
	ACADL	ENST00000862330.1		c.570+11A>G		intron	N/A	ENSP00000532389.1
	ACADL	ENST00000862329.1		c.465+11A>G		intron	N/A	ENSP00000532388.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41641 AN: 152010 Hom.: 6398 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.302 AC: 75713 AN: 251110 AF XY: 0.307

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.335 AC: 486473 AN: 1450052 Hom.: 84427 Cov.: 29 AF XY: 0.335 AC XY: 242019 AN XY: 722120

African (AFR) AF: 0.136 AC: 4525 AN: 33312

American (AMR) AF: 0.228 AC: 10190 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 7385 AN: 26020

East Asian (EAS) AF: 0.194 AC: 7677 AN: 39524

South Asian (SAS) AF: 0.308 AC: 26515 AN: 86036

European-Finnish (FIN) AF: 0.373 AC: 19844 AN: 53244

Middle Eastern (MID) AF: 0.207 AC: 1183 AN: 5728

European-Non Finnish (NFE) AF: 0.354 AC: 390376 AN: 1101486

Other (OTH) AF: 0.313 AC: 18778 AN: 60026

GnomAD4 genome AF: 0.274 AC: 41639 AN: 152128 Hom.: 6401 Cov.: 32 AF XY: 0.272 AC XY: 20202 AN XY: 74378

African (AFR) AF: 0.142 AC: 5905 AN: 41524

American (AMR) AF: 0.251 AC: 3833 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3466

East Asian (EAS) AF: 0.201 AC: 1037 AN: 5172

South Asian (SAS) AF: 0.296 AC: 1424 AN: 4814

European-Finnish (FIN) AF: 0.359 AC: 3790 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23705 AN: 67978

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.316 Hom.: 26625

Bravo AF: 0.261

Asia WGS AF: 0.239 AC: 833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.61
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3764913; hg19: chr2-211074909; COSMIC: COSV52052639;