rs6569480

Positions:

• chr6-127300603-A-G
• chr6-127300603-A-T

Variant summary

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

The NM_001002030.2(ECHDC1):​c.498-10326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,032 control chromosomes in the GnomAD database, including 40,740 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 0.73 (40740 hom., cov: 31)
• Consequence: ECHDC1 NM_001002030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

Genes affected

ECHDC1 (HGNC:21489): (ethylmalonyl-CoA decarboxylase 1) Predicted to enable carboxy-lyase activity and enoyl-CoA hydratase activity. Predicted to be involved in fatty acid beta-oxidation. Predicted to be integral component of membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECHDC1	NM_001002030.2	c.498-10326T>C		intron_variant		ENST00000454859.8	NP_001002030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECHDC1	ENST00000454859.8	c.498-10326T>C		intron_variant		1	NM_001002030.2	ENSP00000401751	P2

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110975 AN: 151914 Hom.: 40714 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.730 AC: 111050 AN: 152032 Hom.: 40740 Cov.: 31 AF XY: 0.725 AC XY: 53866 AN XY: 74298

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.753

Alfa AF: 0.745 Hom.: 15236

Bravo AF: 0.734

Asia WGS AF: 0.690 AC: 2402 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6569480; hg19: chr6-127621748;