12-111757172-T-C

Variant names:

• chr12-111757172-T-C
• rs737280
• ENST00000546840.3:c.102+1427T>C

Variant summary

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

The ENST00000546840.3(ENSG00000257767):​c.102+1427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 338,786 control chromosomes in the GnomAD database, including 37,303 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 0.46 (20271 hom., cov: 32)
  • Exomes 𝑓: 0.38 (17032 hom.)
• Consequence: ENSG00000257767 ENST00000546840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76
• Publications: 24 publications found

Genes affected

ENSG00000257767 (HGNC:):

ACAD10 (HGNC:21597): (acyl-CoA dehydrogenase family member 10) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes (ACADs), which participate in the beta-oxidation of fatty acids in mitochondria. The encoded enzyme contains a hydrolase domain at the N-terminal portion, a serine/threonine protein kinase catlytic domain in the central region, and a conserved ACAD domain at the C-terminus. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Nov 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000546840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD10	NM_025247.6	MANE Select	c.*699T>C		downstream_gene	N/A	NP_079523.3
	ACAD10	NM_001136538.2		c.*699T>C		downstream_gene	N/A	NP_001130010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000257767	ENST00000546840.3	TSL:5	c.102+1427T>C		intron	N/A	ENSP00000450353.4
	ACAD10	ENST00000313698.9	TSL:1 MANE Select	c.*699T>C		downstream_gene	N/A	ENSP00000325137.5
	ACAD10	ENST00000455480.6	TSL:1	c.*699T>C		downstream_gene	N/A	ENSP00000389813.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69328 AN: 151904 Hom.: 20216 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.383 AC: 71608 AN: 186764 Hom.: 17032 AF XY: 0.409 AC XY: 41811 AN XY: 102228

African (AFR) AF: 0.774 AC: 3659 AN: 4728

American (AMR) AF: 0.448 AC: 3978 AN: 8870

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 706 AN: 4242

East Asian (EAS) AF: 0.907 AC: 6299 AN: 6942

South Asian (SAS) AF: 0.581 AC: 22972 AN: 39518

European-Finnish (FIN) AF: 0.248 AC: 2114 AN: 8510

Middle Eastern (MID) AF: 0.410 AC: 267 AN: 652

European-Non Finnish (NFE) AF: 0.274 AC: 28647 AN: 104440

Other (OTH) AF: 0.335 AC: 2966 AN: 8862

GnomAD4 genome AF: 0.457 AC: 69448 AN: 152022 Hom.: 20271 Cov.: 32 AF XY: 0.461 AC XY: 34232 AN XY: 74304

African (AFR) AF: 0.781 AC: 32371 AN: 41460

American (AMR) AF: 0.433 AC: 6610 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4646 AN: 5160

South Asian (SAS) AF: 0.599 AC: 2882 AN: 4808

European-Finnish (FIN) AF: 0.232 AC: 2448 AN: 10570

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18640 AN: 67954

Other (OTH) AF: 0.433 AC: 914 AN: 2112

Alfa AF: 0.315 Hom.: 12796

Bravo AF: 0.486

Asia WGS AF: 0.712 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.33
PhyloP100		-3.8

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: rs737280; hg19: chr12-112194976; COSMIC: COSV58158260; COSMIC: COSV58158260;