rs11161510

Positions:

• chr1-75744604-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370841.9(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 ENST00000370841.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACADM	NM_000016.6	c.600-1202C>T		intron_variant		ENST00000370841.9	NP_000007.1
DLSTP1	NR_130749.1	n.410G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9	c.600-1202C>T		intron_variant		1	NM_000016.6	ENSP00000359878	P4
DLSTP1	ENST00000444241.1	n.173G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0301

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.257

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

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.242

Alfa AF: 0.284 Hom.: 5950

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11161510; hg19: chr1-76210289; COSMIC: COSV57714347; COSMIC: COSV57714347;