1-75732624-T-C

Variant names:

• chr1-75732624-T-C
• rs74090724
• NM_000016.6:c.119-20T>C

Variant summary

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

The NM_000016.6(ACADM):​c.119-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,591,448 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (273 hom., cov: 33)
  • Exomes 𝑓: 0.029 (842 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.109
• Publications: 0 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-75732624-T-C is Benign according to our data. Variant chr1-75732624-T-C is described in ClinVar as Benign. ClinVar VariationId is 92256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000016.6. 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
	ACADM	NM_000016.6	MANE Select	c.119-20T>C		intron	N/A	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.119-20T>C		intron	N/A	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.131-20T>C		intron	N/A	NP_001120800.1	P11310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.119-20T>C		intron	N/A	ENSP00000359878.5	P11310-1
	ACADM	ENST00000370834.9	TSL:1	c.119-20T>C		intron	N/A	ENSP00000359871.5	Q5T4U5
	ACADM	ENST00000420607.6	TSL:1	c.131-20T>C		intron	N/A	ENSP00000409612.2	P11310-2

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7446 AN: 152156 Hom.: 271 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0268 AC: 6701 AN: 250496 AF XY: 0.0250

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0245

Gnomad ASJ exome AF: 0.00467

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0203

Gnomad NFE exome AF: 0.0285

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0292 AC: 41984 AN: 1439174 Hom.: 842 Cov.: 27 AF XY: 0.0282 AC XY: 20254 AN XY: 717528

African (AFR) AF: 0.112 AC: 3677 AN: 32940

American (AMR) AF: 0.0255 AC: 1139 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00435 AC: 113 AN: 25966

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39532

South Asian (SAS) AF: 0.00804 AC: 690 AN: 85826

European-Finnish (FIN) AF: 0.0197 AC: 1052 AN: 53396

Middle Eastern (MID) AF: 0.00787 AC: 45 AN: 5716

European-Non Finnish (NFE) AF: 0.0307 AC: 33526 AN: 1091510

Other (OTH) AF: 0.0292 AC: 1740 AN: 59606

GnomAD4 genome AF: 0.0490 AC: 7462 AN: 152274 Hom.: 273 Cov.: 33 AF XY: 0.0474 AC XY: 3529 AN XY: 74460

African (AFR) AF: 0.109 AC: 4509 AN: 41548

American (AMR) AF: 0.0352 AC: 539 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4832

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0296 AC: 2016 AN: 68016

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0373 Hom.: 34

Bravo AF: 0.0527

Asia WGS AF: 0.0110 AC: 38 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.75
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs74090724; hg19: chr1-76198309; COSMIC: COSV63720161; COSMIC: COSV63720161;