6-4125421-A-G

Position:

• chr6-4125421-A-G

Variant summary

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

The NM_206836.3(ECI2):​c.675-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,608,078 control chromosomes in the GnomAD database, including 78,978 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 0.30 (7083 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71895 hom.)
• Consequence: ECI2 NM_206836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

TEX56P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECI2	NM_206836.3	c.675-51T>C		intron_variant		ENST00000380118.8	NP_996667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECI2	ENST00000380118.8	c.675-51T>C		intron_variant		1	NM_206836.3	ENSP00000369461.3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45945 AN: 152070 Hom.: 7079 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.328

GnomAD3 exomes AF: 0.303 AC: 74433 AN: 245752 Hom.: 11469 AF XY: 0.300 AC XY: 40039 AN XY: 133274

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.313 AC: 455456 AN: 1455890 Hom.: 71895 Cov.: 32 AF XY: 0.310 AC XY: 224759 AN XY: 724208

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.302 AC: 45973 AN: 152188 Hom.: 7083 Cov.: 33 AF XY: 0.298 AC XY: 22209 AN XY: 74424

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.327

Alfa AF: 0.309 Hom.: 13101

Bravo AF: 0.312

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.57

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: rs659305; hg19: chr6-4125655; COSMIC: COSV60985094; COSMIC: COSV60985094;