1-75728544-GTT-GT

Variant names:

• chr1-75728544-GT-G
• rs796117827
• NM_000016.6:c.118+60delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000016.6(ACADM):​c.118+60delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,252,014 control chromosomes in the GnomAD database, including 625,989 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76150 hom., cov: 0)
  • Exomes 𝑓: 1.0 (549839 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 1-75728544-GT-G is Benign according to our data. Variant chr1-75728544-GT-G is described in ClinVar as Benign. ClinVar VariationId is 226050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.118+60delT		intron	N/A	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.118+60delT		intron	N/A	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.130+60delT		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.118+57delT		intron	N/A	ENSP00000359878.5	P11310-1
	ACADM	ENST00000370834.9	TSL:1	c.118+57delT		intron	N/A	ENSP00000359871.5	Q5T4U5
	ACADM	ENST00000420607.6	TSL:1	c.130+57delT		intron	N/A	ENSP00000409612.2	P11310-2

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152183 AN: 152184 Hom.: 76091 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1099695 AN: 1099712 Hom.: 549839 AF XY: 1.00 AC XY: 564305 AN XY: 564320

African (AFR) AF: 1.00 AC: 26160 AN: 26160

American (AMR) AF: 1.00 AC: 43878 AN: 43878

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23692 AN: 23692

East Asian (EAS) AF: 1.00 AC: 37456 AN: 37456

South Asian (SAS) AF: 1.00 AC: 78358 AN: 78358

European-Finnish (FIN) AF: 1.00 AC: 49534 AN: 49534

Middle Eastern (MID) AF: 1.00 AC: 5072 AN: 5072

European-Non Finnish (NFE) AF: 1.00 AC: 787289 AN: 787306

Other (OTH) AF: 1.00 AC: 48256 AN: 48256

GnomAD4 genome AF: 1.00 AC: 152301 AN: 152302 Hom.: 76150 Cov.: 0 AF XY: 1.00 AC XY: 74459 AN XY: 74460

African (AFR) AF: 1.00 AC: 41565 AN: 41566

American (AMR) AF: 1.00 AC: 15304 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10602 AN: 10602

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68032 AN: 68032

Other (OTH) AF: 1.00 AC: 2112 AN: 2112

Alfa AF: 1.00 Hom.: 9297

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3470 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
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: rs796117827; hg19: chr1-76194229;