rs6739874

Positions:

• chr2-210196946-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000233710.4(ACADL):​c.985-1608C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 152,210 control chromosomes in the GnomAD database, including 66 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 0.016 (66 hom., cov: 32)
• Consequence: ACADL ENST00000233710.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADL	NM_001608.4	c.985-1608C>A		intron_variant		ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.922-1608C>A		intron_variant			XP_005246574.1
ACADL	XM_047444103.1	c.562-1608C>A		intron_variant			XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.985-1608C>A		intron_variant		1	NM_001608.4	ENSP00000233710	P1
	ENST00000639259.2	n.279+25117G>T		intron_variant, non_coding_transcript_variant		5
	ENST00000412065.1	n.313-21526G>T		intron_variant, non_coding_transcript_variant		4
ACADL	ENST00000652584.1	n.1213-1608C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2477 AN: 152092 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0162 AC: 2473 AN: 152210 Hom.: 66 Cov.: 32 AF XY: 0.0163 AC XY: 1215 AN XY: 74422

Gnomad4 AFR AF: 0.0565

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0164 Hom.: 10

Bravo AF: 0.0185

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs6739874; hg19: chr2-211061670;