chr6-127329221-C-G

Variant names:

• chr6-127329221-C-G
• rs17054536
• NM_001002030.2:c.220+1588G>C

Variant summary

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

The NM_001002030.2(ECHDC1):​c.220+1588G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 151,712 control chromosomes in the GnomAD database, including 390 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 0.070 (390 hom., cov: 32)
• Consequence: ECHDC1 NM_001002030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 1 publications found

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]

LOC105377994 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002030.2. 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
	ECHDC1	NM_001002030.2	MANE Select	c.220+1588G>C		intron	N/A	NP_001002030.1
	ECHDC1	NM_001139510.2		c.238+1588G>C		intron	N/A	NP_001132982.1
	ECHDC1	NM_001105544.2		c.-5-2077G>C		intron	N/A	NP_001099014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECHDC1	ENST00000454859.8	TSL:1 MANE Select	c.220+1588G>C		intron	N/A	ENSP00000401751.3
	ECHDC1	ENST00000528402.5	TSL:1	c.-5-2077G>C		intron	N/A	ENSP00000436109.1
	ECHDC1	ENST00000436638.6	TSL:3	c.220+1588G>C		intron	N/A	ENSP00000399233.2

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10555 AN: 151596 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0706

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

GnomAD4 genome AF: 0.0697 AC: 10577 AN: 151712 Hom.: 390 Cov.: 32 AF XY: 0.0687 AC XY: 5095 AN XY: 74124

African (AFR) AF: 0.0805 AC: 3330 AN: 41352

American (AMR) AF: 0.0531 AC: 810 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.0527 AC: 272 AN: 5162

South Asian (SAS) AF: 0.0973 AC: 467 AN: 4800

European-Finnish (FIN) AF: 0.0557 AC: 582 AN: 10444

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4535 AN: 67930

Other (OTH) AF: 0.0722 AC: 152 AN: 2104

Alfa AF: 0.0198 Hom.: 12

Bravo AF: 0.0692

Asia WGS AF: 0.0920 AC: 318 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.56
PhyloP100		-2.3
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: rs17054536; hg19: chr6-127650366;