rs17848065

Variant names:

• chr1-75762802-G-A
• rs17848065
• ENST00000526196.5:n.*1073G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-75762802-G-A
• chr1-75762802-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000526196.5(ACADM):​n.*1073G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,288,190 control chromosomes in the GnomAD database, including 1,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (140 hom., cov: 33)
  • Exomes 𝑓: 0.036 (890 hom.)
• Consequence: ACADM ENST00000526196.5 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.92
• Publications: 3 publications found

Genes affected

ACADM (HGNC:89): (acyl-CoA dehydrogenase medium chain) This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACADM Gene-Disease associations (from GenCC):

• medium chain acyl-CoA dehydrogenase deficiency

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-75762802-G-A is Benign according to our data. Variant chr1-75762802-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526196.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	NM_000016.6	MANE Select	c.*39G>A		3_prime_UTR	Exon 12 of 12	NP_000007.1
	ACADM	NM_001286043.2		c.*39G>A		3_prime_UTR	Exon 13 of 13	NP_001272972.1
	ACADM	NM_001127328.3		c.*39G>A		3_prime_UTR	Exon 12 of 12	NP_001120800.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000526196.5	TSL:1	n.*1073G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000431953.1
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.*39G>A		3_prime_UTR	Exon 12 of 12	ENSP00000359878.5
	ACADM	ENST00000370834.9	TSL:1	c.*39G>A		3_prime_UTR	Exon 13 of 13	ENSP00000359871.5

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5972 AN: 151974 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0412

GnomAD2 exomes AF: 0.0355 AC: 7969 AN: 224584 AF XY: 0.0355

Gnomad AFR exome AF: 0.0358

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.00604

Gnomad FIN exome AF: 0.0591

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.0389

GnomAD4 exome AF: 0.0360 AC: 40866 AN: 1136098 Hom.: 890 Cov.: 15 AF XY: 0.0361 AC XY: 20930 AN XY: 579168

African (AFR) AF: 0.0368 AC: 971 AN: 26396

American (AMR) AF: 0.0247 AC: 1045 AN: 42244

Ashkenazi Jewish (ASJ) AF: 0.0307 AC: 725 AN: 23652

East Asian (EAS) AF: 0.00554 AC: 208 AN: 37576

South Asian (SAS) AF: 0.0307 AC: 2332 AN: 75874

European-Finnish (FIN) AF: 0.0599 AC: 3112 AN: 51990

Middle Eastern (MID) AF: 0.0586 AC: 298 AN: 5088

European-Non Finnish (NFE) AF: 0.0368 AC: 30337 AN: 824138

Other (OTH) AF: 0.0374 AC: 1838 AN: 49140

GnomAD4 genome AF: 0.0393 AC: 5974 AN: 152092 Hom.: 140 Cov.: 33 AF XY: 0.0393 AC XY: 2919 AN XY: 74368

African (AFR) AF: 0.0365 AC: 1515 AN: 41512

American (AMR) AF: 0.0380 AC: 580 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 115 AN: 3468

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5180

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4824

European-Finnish (FIN) AF: 0.0590 AC: 624 AN: 10568

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0403 AC: 2737 AN: 67946

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0382 Hom.: 41

Bravo AF: 0.0371

Asia WGS AF: 0.0250 AC: 86 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Medium-chain acyl-coenzyme A dehydrogenase deficiency (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17848065; hg19: chr1-76228487;