rs17848068

Variant names:

• chr1-75724531-G-A
• rs17848068
• ENST00000541113.6:c.-257G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-75724531-G-A
• chr1-75724531-G-T

Variant summary

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

The ENST00000541113.6(ACADM):​c.-257G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 411,780 control chromosomes in the GnomAD database, including 16,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5739 hom., cov: 31)
  • Exomes 𝑓: 0.28 (10987 hom.)
• Consequence: ACADM ENST00000541113.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.23
• Publications: 7 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ENSG00000293044 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-75724531-G-A is Benign according to our data. Variant chr1-75724531-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 298063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541113.6. 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.-257G>A		upstream_gene	N/A	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.-257G>A		upstream_gene	N/A	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.-257G>A		upstream_gene	N/A	NP_001120800.1	P11310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000541113.6	TSL:1	c.-257G>A		5_prime_UTR	Exon 1 of 11	ENSP00000442324.2	F6YB23
	ACADM	ENST00000680805.1		c.-257G>A		5_prime_UTR	Exon 1 of 11	ENSP00000505447.1	A0A7P0T932
	ACADM	ENST00000680964.1		c.-257G>A		5_prime_UTR	Exon 1 of 12	ENSP00000505961.1	A0A7P0TB51

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40880 AN: 151966 Hom.: 5738 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.276 AC: 71619 AN: 259696 Hom.: 10987 Cov.: 2 AF XY: 0.276 AC XY: 37174 AN XY: 134446

African (AFR) AF: 0.263 AC: 1855 AN: 7042

American (AMR) AF: 0.223 AC: 1614 AN: 7234

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 3897 AN: 9300

East Asian (EAS) AF: 0.0470 AC: 1060 AN: 22532

South Asian (SAS) AF: 0.218 AC: 2256 AN: 10358

European-Finnish (FIN) AF: 0.330 AC: 7161 AN: 21698

Middle Eastern (MID) AF: 0.368 AC: 472 AN: 1284

European-Non Finnish (NFE) AF: 0.297 AC: 48611 AN: 163678

Other (OTH) AF: 0.283 AC: 4693 AN: 16570

GnomAD4 genome AF: 0.269 AC: 40878 AN: 152084 Hom.: 5739 Cov.: 31 AF XY: 0.268 AC XY: 19924 AN XY: 74310

African (AFR) AF: 0.261 AC: 10837 AN: 41516

American (AMR) AF: 0.233 AC: 3558 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3472

East Asian (EAS) AF: 0.0249 AC: 128 AN: 5136

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4816

European-Finnish (FIN) AF: 0.319 AC: 3378 AN: 10590

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19635 AN: 67948

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.159 Hom.: 338

Bravo AF: 0.264

Asia WGS AF: 0.131 AC: 456 AN: 3476

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)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.86
PhyloP100		-2.2
PromoterAI		0.065	Neutral
Mutation Taster		=300/0	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: rs17848068; hg19: chr1-76190216;