rs8064573

Variant names:

• chr17-7222826-G-A
• rs8064573
• NM_000018.4:c.1038G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7222826-G-A
• chr17-7222826-G-T
• chr17-7222826-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BA1 BP4 BP7

This summary comes from the ClinGen Evidence Repository: The c.1038G>A variant in ACADVL is a synonymous variant which occurs in exon 10. The highest population minor allele frequency in gnomAD v2.1.1 is 0.08089 in the African/African American population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.007) for BA1, and therefore meets this criterion (BA1). The results from 2 in silico splicing predictors (SpliceAI, MutationTaster) support that this variant does not affect splicing. In addition, it occurs at a nucleotide that is not conserved as shown by the 100 vertebrate Basewise Conservation by PhyloP track in the UCSC genome browser (BP4, BP7). In summary, this variant meets the criteria to be classified as benign for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: BA1, BP4, BP7 (VCEP specifications v2.0, approved on 09/16/2021). LINK:https://erepo.genome.network/evrepo/ui/classification/CA145601/MONDO:0008723/021

• Frequency:
  • Genomes: 𝑓 0.022 (149 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (134 hom.)
• Consequence: ACADVL NM_000018.4 synonymous
• Clinical Significance: Benign reviewed by expert panel B:10
• Conservation: PhyloP100: -2.70
• Publications: 4 publications found

Genes affected

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000018.4. 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
	ACADVL	NM_000018.4	MANE Select	c.1038G>A	p.Ala346Ala	synonymous	Exon 10 of 20	NP_000009.1	P49748-1
	ACADVL	NM_001270447.2		c.1107G>A	p.Ala369Ala	synonymous	Exon 11 of 21	NP_001257376.1	P49748-3
	ACADVL	NM_001033859.3		c.972G>A	p.Ala324Ala	synonymous	Exon 9 of 19	NP_001029031.1	P49748-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADVL	ENST00000356839.10	TSL:1 MANE Select	c.1038G>A	p.Ala346Ala	synonymous	Exon 10 of 20	ENSP00000349297.5	P49748-1
	ACADVL	ENST00000350303.9	TSL:1	c.972G>A	p.Ala324Ala	synonymous	Exon 9 of 19	ENSP00000344152.5	P49748-2
	ACADVL	ENST00000543245.6	TSL:2	c.1107G>A	p.Ala369Ala	synonymous	Exon 11 of 21	ENSP00000438689.2	P49748-3

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3390 AN: 152066 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00864

GnomAD2 exomes AF: 0.00642 AC: 1613 AN: 251082 AF XY: 0.00473

Gnomad AFR exome AF: 0.0850

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00257 AC: 3748 AN: 1461020 Hom.: 134 Cov.: 32 AF XY: 0.00220 AC XY: 1601 AN XY: 726832

African (AFR) AF: 0.0869 AC: 2907 AN: 33466

American (AMR) AF: 0.00559 AC: 250 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53210

Middle Eastern (MID) AF: 0.00419 AC: 22 AN: 5248

European-Non Finnish (NFE) AF: 0.000211 AC: 235 AN: 1111992

Other (OTH) AF: 0.00529 AC: 319 AN: 60340

GnomAD4 genome AF: 0.0223 AC: 3388 AN: 152184 Hom.: 149 Cov.: 32 AF XY: 0.0213 AC XY: 1585 AN XY: 74410

African (AFR) AF: 0.0771 AC: 3198 AN: 41488

American (AMR) AF: 0.00954 AC: 146 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67998

Other (OTH) AF: 0.00855 AC: 18 AN: 2106

Alfa AF: 0.00902 Hom.: 64

Bravo AF: 0.0261

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	5	Very long chain acyl-CoA dehydrogenase deficiency (5)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.30
DANN	Benign	0.81
PhyloP100		-2.7
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8064573; hg19: chr17-7126145;