6-4133621-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECI2	NM_206836.3	c.141G>A	p.Met47Ile	missense_variant	Exon 2 of 10	ENST00000380118.8	NP_996667.2
ECI2	NM_001166010.2	c.51G>A	p.Met17Ile	missense_variant	Exon 2 of 10		NP_001159482.1
ECI2	NM_006117.3	c.51G>A	p.Met17Ile	missense_variant	Exon 2 of 10		NP_006108.2
ECI2	NR_028588.2	n.146G>A		non_coding_transcript_exon_variant	Exon 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECI2	ENST00000380118.8	c.141G>A	p.Met47Ile	missense_variant	Exon 2 of 10	1	NM_206836.3	ENSP00000369461.3

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

GnomAD3 exomes AF: 0.197 AC: 49428 AN: 250752 Hom.: 5568 AF XY: 0.200 AC XY: 27046 AN XY: 135560

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 SAS exome AF: 0.131

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

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.0148

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.224

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0239

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.228

Alfa AF: 0.238 Hom.: 11770

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 v4.3

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;.;.;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.10	T;.;.;T;T
MetaRNN	Benign	0.0024	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.067
Sift	Benign	0.41	T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3177253; hg19: chr6-4133855;