6-4125707-A-G

Variant names:

• chr6-4125707-A-G
• rs660560
• NM_206836.3:c.675-337T>C

Variant summary

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

The NM_206836.3(ECI2):​c.675-337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 417,878 control chromosomes in the GnomAD database, including 20,151 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 0.32 (7970 hom., cov: 33)
  • Exomes 𝑓: 0.30 (12181 hom.)
• Consequence: ECI2 NM_206836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	NM_206836.3	MANE Select	c.675-337T>C		intron	N/A	NP_996667.2	O75521-1
	ECI2	NM_001166010.2		c.585-337T>C		intron	N/A	NP_001159482.1	A0A0C4DGA2
	ECI2	NM_006117.3		c.585-337T>C		intron	N/A	NP_006108.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.675-337T>C		intron	N/A	ENSP00000369461.3	O75521-1
	ECI2	ENST00000361538.6	TSL:1	c.585-337T>C		intron	N/A	ENSP00000354737.2	A0A0C4DGA2
	ECI2	ENST00000380125.6	TSL:1	c.585-337T>C		intron	N/A	ENSP00000369468.2	A0A0C4DGA2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48766 AN: 152018 Hom.: 7963 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.298 AC: 79175 AN: 265742 Hom.: 12181 Cov.: 2 AF XY: 0.294 AC XY: 41969 AN XY: 142560

African (AFR) AF: 0.351 AC: 2826 AN: 8060

American (AMR) AF: 0.360 AC: 3940 AN: 10946

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 1950 AN: 7612

East Asian (EAS) AF: 0.372 AC: 4898 AN: 13170

South Asian (SAS) AF: 0.249 AC: 9668 AN: 38848

European-Finnish (FIN) AF: 0.251 AC: 3303 AN: 13148

Middle Eastern (MID) AF: 0.303 AC: 751 AN: 2476

European-Non Finnish (NFE) AF: 0.303 AC: 47461 AN: 156822

Other (OTH) AF: 0.299 AC: 4378 AN: 14660

GnomAD4 genome AF: 0.321 AC: 48805 AN: 152136 Hom.: 7970 Cov.: 33 AF XY: 0.316 AC XY: 23518 AN XY: 74368

African (AFR) AF: 0.351 AC: 14570 AN: 41510

American (AMR) AF: 0.366 AC: 5603 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.363 AC: 1872 AN: 5156

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2765 AN: 10592

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20877 AN: 67982

Other (OTH) AF: 0.341 AC: 720 AN: 2112

Alfa AF: 0.309 Hom.: 3896

Bravo AF: 0.334

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.52
PhyloP100		0.60
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: rs660560; hg19: chr6-4125941; COSMIC: COSV107362338; COSMIC: COSV107362338;