6-4133621-C-T

Variant names:

• chr6-4133621-C-T
• rs3177253
• NM_206836.3:c.141G>A

Variant summary

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

The NM_206836.3(ECI2):​c.141G>A​(p.Met47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,612,960 control chromosomes in the GnomAD database, including 47,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M47V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.20 (3398 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43859 hom.)
• Consequence: ECI2 NM_206836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 43 publications found

Genes affected

ECI2 (HGNC:14601): (enoyl-CoA delta isomerase 2) This gene encodes a member of the hydratase/isomerase superfamily. The protein encoded is a key mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids. It catalyzes the transformation of 3-cis and 3-trans-enoyl-CoA esters arising during the stepwise degradation of cis-, mono-, and polyunsaturated fatty acids to the 2-trans-enoyl-CoA intermediates. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023780167).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206836.3. 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
	ECI2	NM_206836.3	MANE Select	c.141G>A	p.Met47Ile	missense	Exon 2 of 10	NP_996667.2
	ECI2	NM_001166010.2		c.51G>A	p.Met17Ile	missense	Exon 2 of 10	NP_001159482.1
	ECI2	NM_006117.3		c.51G>A	p.Met17Ile	missense	Exon 2 of 10	NP_006108.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.141G>A	p.Met47Ile	missense	Exon 2 of 10	ENSP00000369461.3
	ECI2	ENST00000361538.6	TSL:1	c.51G>A	p.Met17Ile	missense	Exon 2 of 10	ENSP00000354737.2
	ECI2	ENST00000380125.6	TSL:1	c.51G>A	p.Met17Ile	missense	Exon 2 of 10	ENSP00000369468.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30047 AN: 151984 Hom.: 3403 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.197 AC: 49428 AN: 250752 AF XY: 0.200

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0253

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.238 AC: 348395 AN: 1460858 Hom.: 43859 Cov.: 34 AF XY: 0.236 AC XY: 171277 AN XY: 726708

African (AFR) AF: 0.117 AC: 3928 AN: 33460

American (AMR) AF: 0.188 AC: 8389 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5716 AN: 26106

East Asian (EAS) AF: 0.0148 AC: 589 AN: 39672

South Asian (SAS) AF: 0.134 AC: 11511 AN: 86096

European-Finnish (FIN) AF: 0.222 AC: 11839 AN: 53390

Middle Eastern (MID) AF: 0.224 AC: 1292 AN: 5760

European-Non Finnish (NFE) AF: 0.262 AC: 291597 AN: 1111476

Other (OTH) AF: 0.224 AC: 13534 AN: 60348

GnomAD4 genome AF: 0.198 AC: 30046 AN: 152102 Hom.: 3398 Cov.: 32 AF XY: 0.192 AC XY: 14286 AN XY: 74378

African (AFR) AF: 0.121 AC: 5007 AN: 41486

American (AMR) AF: 0.192 AC: 2935 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3466

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5186

South Asian (SAS) AF: 0.131 AC: 632 AN: 4832

European-Finnish (FIN) AF: 0.232 AC: 2457 AN: 10572

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17410 AN: 67970

Other (OTH) AF: 0.228 AC: 481 AN: 2110

Alfa AF: 0.232 Hom.: 22025

Bravo AF: 0.193

TwinsUK AF: 0.263 AC: 977

ALSPAC AF: 0.266 AC: 1027

ESP6500AA AF: 0.123 AC: 544

ESP6500EA AF: 0.249 AC: 2144

ExAC AF: 0.196 AC: 23749

Asia WGS AF: 0.0900 AC: 315 AN: 3478

EpiCase AF: 0.262

EpiControl AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.067
Sift	Benign	0.41	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.23		Loss of disorder (P = 0.0277)
MPC		0.068
ClinPred		0.0063	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.25
Mutation Taster		=97/3	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: rs3177253; hg19: chr6-4133855; COSMIC: COSV107362339; COSMIC: COSV107362339;