chr2-210210185-T-C

Position:

• chr2-210210185-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADL	NM_001608.4	c.603+11A>G		intron_variant		ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.540+11A>G		intron_variant			XP_005246574.1
ACADL	XM_047444103.1	c.180+11A>G		intron_variant			XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.603+11A>G		intron_variant		1	NM_001608.4	ENSP00000233710.3

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

GnomAD3 exomes AF: 0.302 AC: 75713 AN: 251110 Hom.: 12152 AF XY: 0.307 AC XY: 41660 AN XY: 135730

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 SAS exome AF: 0.309

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

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.313

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.279

Alfa AF: 0.325 Hom.: 12231

Bravo AF: 0.261

Asia WGS AF: 0.239 AC: 833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764913; hg19: chr2-211074909; COSMIC: COSV52052639;