rs11961994

Variant names:

• chr6-127328205-C-T
• rs11961994
• NM_001002030.2:c.221-1061G>A

Variant summary

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

The NM_001002030.2(ECHDC1):​c.221-1061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,148 control chromosomes in the GnomAD database, including 24,216 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 0.54 (24216 hom., cov: 33)
• Consequence: ECHDC1 NM_001002030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECHDC1	NM_001002030.2	MANE Select	c.221-1061G>A		intron	N/A	NP_001002030.1	Q9NTX5-2
	ECHDC1	NM_001139510.2		c.239-1061G>A		intron	N/A	NP_001132982.1	Q9NTX5-1
	ECHDC1	NM_001105544.2		c.-5-1061G>A		intron	N/A	NP_001099014.1	Q9NTX5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECHDC1	ENST00000454859.8	TSL:1 MANE Select	c.221-1061G>A		intron	N/A	ENSP00000401751.3	Q9NTX5-2
	ECHDC1	ENST00000528402.5	TSL:1	c.-5-1061G>A		intron	N/A	ENSP00000436109.1	Q9NTX5-4
	ECHDC1	ENST00000436638.6	TSL:3	c.221-1061G>A		intron	N/A	ENSP00000399233.2	H0Y5L2

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81942 AN: 152028 Hom.: 24209 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.539 AC: 81956 AN: 152148 Hom.: 24216 Cov.: 33 AF XY: 0.529 AC XY: 39314 AN XY: 74368

African (AFR) AF: 0.356 AC: 14766 AN: 41526

American (AMR) AF: 0.464 AC: 7102 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2362 AN: 3470

East Asian (EAS) AF: 0.101 AC: 522 AN: 5184

South Asian (SAS) AF: 0.481 AC: 2319 AN: 4826

European-Finnish (FIN) AF: 0.642 AC: 6781 AN: 10566

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46169 AN: 67974

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

Alfa AF: 0.618 Hom.: 73712

Bravo AF: 0.516

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-1.5
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: rs11961994; hg19: chr6-127649350;