1-75728369-C-G

Variant names:

• chr1-75728369-C-G
• rs7524467
• NM_000016.6:c.31-32C>G

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.31-32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,560,352 control chromosomes in the GnomAD database, including 62,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4862 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57623 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.313
• Publications: 16 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=-0.5).
• BP6: Variant 1-75728369-C-G is Benign according to our data. Variant chr1-75728369-C-G is described in ClinVar as Benign. ClinVar VariationId is 254691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	NM_000016.6	MANE Select	c.31-32C>G		intron	N/A	NP_000007.1
	ACADM	NM_001286043.2		c.31-32C>G		intron	N/A	NP_001272972.1
	ACADM	NM_001127328.3		c.31-20C>G		intron	N/A	NP_001120800.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.31-32C>G		intron	N/A	ENSP00000359878.5
	ACADM	ENST00000370834.9	TSL:1	c.31-32C>G		intron	N/A	ENSP00000359871.5
	ACADM	ENST00000420607.6	TSL:1	c.31-20C>G		intron	N/A	ENSP00000409612.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36816 AN: 151892 Hom.: 4863 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.246 AC: 60819 AN: 246760 AF XY: 0.246

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.0259

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.280 AC: 394000 AN: 1408342 Hom.: 57623 Cov.: 23 AF XY: 0.277 AC XY: 194568 AN XY: 703348

African (AFR) AF: 0.152 AC: 4869 AN: 32090

American (AMR) AF: 0.284 AC: 12436 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5393 AN: 25560

East Asian (EAS) AF: 0.0303 AC: 1190 AN: 39246

South Asian (SAS) AF: 0.188 AC: 15791 AN: 83928

European-Finnish (FIN) AF: 0.261 AC: 13710 AN: 52466

Middle Eastern (MID) AF: 0.243 AC: 1365 AN: 5622

European-Non Finnish (NFE) AF: 0.303 AC: 323848 AN: 1067044

Other (OTH) AF: 0.263 AC: 15398 AN: 58542

GnomAD4 genome AF: 0.242 AC: 36826 AN: 152010 Hom.: 4862 Cov.: 32 AF XY: 0.239 AC XY: 17775 AN XY: 74296

African (AFR) AF: 0.150 AC: 6217 AN: 41460

American (AMR) AF: 0.289 AC: 4412 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3470

East Asian (EAS) AF: 0.0350 AC: 181 AN: 5174

South Asian (SAS) AF: 0.193 AC: 931 AN: 4814

European-Finnish (FIN) AF: 0.263 AC: 2771 AN: 10552

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20703 AN: 67956

Other (OTH) AF: 0.249 AC: 524 AN: 2108

Alfa AF: 0.186 Hom.: 553

Bravo AF: 0.239

Asia WGS AF: 0.169 AC: 587 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Medium-chain acyl-coenzyme A dehydrogenase deficiency (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.3
DANN	Benign	0.77
PhyloP100		0.31
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: rs7524467; hg19: chr1-76194054;