12-120726849-C-T

Position:

• chr12-120726849-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000017.4(ACADS):​c.47-177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,144 control chromosomes in the GnomAD database, including 1,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.098 (1899 hom., cov: 32)
• Consequence: ACADS NM_000017.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

Genes affected

ACADS (HGNC:90): (acyl-CoA dehydrogenase short chain) This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-120726849-C-T is Benign according to our data. Variant chr12-120726849-C-T is described in ClinVar as [Benign]. Clinvar id is 1182840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADS	NM_000017.4	c.47-177C>T		intron_variant		ENST00000242592.9
ACADS	NM_001302554.2	c.47-177C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADS	ENST00000242592.9	c.47-177C>T		intron_variant		1	NM_000017.4	P1
ACADS	ENST00000411593.2	c.47-177C>T		intron_variant		2
ACADS	ENST00000539690.1	n.159-177C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 14931 AN: 152026 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00856

Gnomad OTH AF: 0.0636

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0983 AC: 14959 AN: 152144 Hom.: 1899 Cov.: 32 AF XY: 0.0976 AC XY: 7266 AN XY: 74410

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.00856

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0601 Hom.: 156

Bravo AF: 0.112

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11065230; hg19: chr12-121164652;