rs11161510

Variant names:

• chr1-75744604-C-T
• rs11161510
• NM_000016.6:c.600-1202C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000016.6(ACADM):​c.600-1202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,204,448 control chromosomes in the GnomAD database, including 44,485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4597 hom., cov: 32)
  • Exomes 𝑓: 0.27 (39888 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 25 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]

DLSTP1 (HGNC:2912): (dihydrolipoamide S-succinyltransferase pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADM	NM_000016.6	c.600-1202C>T		intron_variant	Intron 7 of 11	ENST00000370841.9	NP_000007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9	c.600-1202C>T		intron_variant	Intron 7 of 11	1	NM_000016.6	ENSP00000359878.5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35850 AN: 151990 Hom.: 4597 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.268 AC: 281879 AN: 1052340 Hom.: 39888 Cov.: 16 AF XY: 0.265 AC XY: 143550 AN XY: 541664

African (AFR) AF: 0.154 AC: 3810 AN: 24736

American (AMR) AF: 0.218 AC: 9586 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4868 AN: 23480

East Asian (EAS) AF: 0.0301 AC: 1134 AN: 37690

South Asian (SAS) AF: 0.184 AC: 14360 AN: 77912

European-Finnish (FIN) AF: 0.256 AC: 13529 AN: 52784

Middle Eastern (MID) AF: 0.244 AC: 1137 AN: 4666

European-Non Finnish (NFE) AF: 0.299 AC: 221463 AN: 740464

Other (OTH) AF: 0.257 AC: 11992 AN: 46574

GnomAD4 genome AF: 0.236 AC: 35859 AN: 152108 Hom.: 4597 Cov.: 32 AF XY: 0.232 AC XY: 17285 AN XY: 74356

African (AFR) AF: 0.148 AC: 6143 AN: 41522

American (AMR) AF: 0.254 AC: 3885 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.0350 AC: 181 AN: 5172

South Asian (SAS) AF: 0.188 AC: 908 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2723 AN: 10560

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

European-Non Finnish (NFE) AF: 0.301 AC: 20438 AN: 67966

Other (OTH) AF: 0.242 AC: 509 AN: 2106

Alfa AF: 0.278 Hom.: 7513

Bravo AF: 0.230

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		2.8
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: rs11161510; hg19: chr1-76210289; COSMIC: COSV57714347; COSMIC: COSV57714347;