rs142795930

Variant names:

• chr1-75728328-T-C
• rs142795930
• NM_000016.6:c.31-73T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-75728328-T-C
• chr1-75728328-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000016.6(ACADM):​c.31-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,257,478 control chromosomes in the GnomAD database, including 559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (60 hom., cov: 32)
  • Exomes 𝑓: 0.026 (499 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.297
• Publications: 0 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=-0.91).
• BP6: Variant 1-75728328-T-C is Benign according to our data. Variant chr1-75728328-T-C is described in ClinVar as Benign. ClinVar VariationId is 226074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3385/152332) while in subpopulation NFE AF = 0.0269 (1833/68032). AF 95% confidence interval is 0.0259. There are 60 homozygotes in GnomAd4. There are 1813 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADM	NM_000016.6	c.31-73T>C		intron_variant	Intron 1 of 11	ENST00000370841.9	NP_000007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9	c.31-73T>C		intron_variant	Intron 1 of 11	1	NM_000016.6	ENSP00000359878.5

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3390 AN: 152214 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0258 AC: 28501 AN: 1105146 Hom.: 499 AF XY: 0.0258 AC XY: 14480 AN XY: 561650

African (AFR) AF: 0.00392 AC: 98 AN: 24986

American (AMR) AF: 0.0148 AC: 571 AN: 38702

Ashkenazi Jewish (ASJ) AF: 0.0390 AC: 859 AN: 22040

East Asian (EAS) AF: 0.0000544 AC: 2 AN: 36754

South Asian (SAS) AF: 0.0249 AC: 1761 AN: 70860

European-Finnish (FIN) AF: 0.0656 AC: 3120 AN: 47548

Middle Eastern (MID) AF: 0.0342 AC: 145 AN: 4234

European-Non Finnish (NFE) AF: 0.0254 AC: 20627 AN: 811926

Other (OTH) AF: 0.0274 AC: 1318 AN: 48096

GnomAD4 genome AF: 0.0222 AC: 3385 AN: 152332 Hom.: 60 Cov.: 32 AF XY: 0.0243 AC XY: 1813 AN XY: 74494

African (AFR) AF: 0.00445 AC: 185 AN: 41574

American (AMR) AF: 0.0194 AC: 297 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 125 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4826

European-Finnish (FIN) AF: 0.0688 AC: 731 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1833 AN: 68032

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0188 Hom.: 12

Bravo AF: 0.0178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:3

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 20, 2015

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.53
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs142795930; hg19: chr1-76194013;