6-4125863-G-A

Variant names:

• chr6-4125863-G-A
• rs661404
• NM_206836.3:c.674+272C>T

Variant summary

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

The NM_206836.3(ECI2):​c.674+272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 550,548 control chromosomes in the GnomAD database, including 54,192 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 0.50 (21819 hom., cov: 33)
  • Exomes 𝑓: 0.39 (32373 hom.)
• Consequence: ECI2 NM_206836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 11 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]

TEX56P (HGNC:):

TEX56P (HGNC:21620): (testis expressed 56, pseudogene)

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 (AFR) allele frequency at 95% confidence interval = 0.78 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.674+272C>T		intron	N/A	NP_996667.2
	TEX56P	NR_104463.3		n.2308G>A		non_coding_transcript_exon	Exon 6 of 8
	TEX56P	NR_104464.3		n.1654G>A		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.674+272C>T		intron	N/A	ENSP00000369461.3
	ECI2	ENST00000361538.6	TSL:1	c.584+272C>T		intron	N/A	ENSP00000354737.2
	ECI2	ENST00000380125.6	TSL:1	c.584+272C>T		intron	N/A	ENSP00000369468.2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76596 AN: 152040 Hom.: 21776 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.406 AC: 40345 AN: 99462 AF XY: 0.395

Gnomad AFR exome AF: 0.802

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.371

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.393 AC: 156578 AN: 398392 Hom.: 32373 Cov.: 2 AF XY: 0.385 AC XY: 84067 AN XY: 218604

African (AFR) AF: 0.789 AC: 9231 AN: 11698

American (AMR) AF: 0.430 AC: 9779 AN: 22768

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 4609 AN: 13658

East Asian (EAS) AF: 0.382 AC: 7749 AN: 20310

South Asian (SAS) AF: 0.303 AC: 15965 AN: 52734

European-Finnish (FIN) AF: 0.388 AC: 8152 AN: 21032

Middle Eastern (MID) AF: 0.367 AC: 1201 AN: 3270

European-Non Finnish (NFE) AF: 0.394 AC: 90900 AN: 230930

Other (OTH) AF: 0.409 AC: 8992 AN: 21992

GnomAD4 genome AF: 0.504 AC: 76698 AN: 152156 Hom.: 21819 Cov.: 33 AF XY: 0.498 AC XY: 37056 AN XY: 74372

African (AFR) AF: 0.787 AC: 32690 AN: 41538

American (AMR) AF: 0.453 AC: 6925 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1884 AN: 5170

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4822

European-Finnish (FIN) AF: 0.403 AC: 4259 AN: 10558

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26937 AN: 67982

Other (OTH) AF: 0.479 AC: 1013 AN: 2114

Alfa AF: 0.459 Hom.: 4009

Bravo AF: 0.523

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.070
DANN	Benign	0.42
PhyloP100		-1.3
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: rs661404; hg19: chr6-4126097; COSMIC: COSV60986713; COSMIC: COSV60986713;