rs9503924

Variant names:

• chr6-4126146-G-A
• rs9503924
• NM_206836.3:c.663C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_206836.3(ECI2):​c.663C>T​(p.Ala221Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,613,478 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: ECI2 NM_206836.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.155
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 6-4126146-G-A is Benign according to our data. Variant chr6-4126146-G-A is described in ClinVar as Benign. ClinVar VariationId is 782468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.155 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0601 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.663C>T	p.Ala221Ala	synonymous	Exon 6 of 10	NP_996667.2	O75521-1
	ECI2	NM_001166010.2		c.573C>T	p.Ala191Ala	synonymous	Exon 6 of 10	NP_001159482.1	A0A0C4DGA2
	ECI2	NM_006117.3		c.573C>T	p.Ala191Ala	synonymous	Exon 6 of 10	NP_006108.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.663C>T	p.Ala221Ala	synonymous	Exon 6 of 10	ENSP00000369461.3	O75521-1
	ECI2	ENST00000361538.6	TSL:1	c.573C>T	p.Ala191Ala	synonymous	Exon 6 of 10	ENSP00000354737.2	A0A0C4DGA2
	ECI2	ENST00000380125.6	TSL:1	c.573C>T	p.Ala191Ala	synonymous	Exon 6 of 10	ENSP00000369468.2	A0A0C4DGA2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2721 AN: 152134 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00450 AC: 1130 AN: 250930 AF XY: 0.00327

Gnomad AFR exome AF: 0.0639

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00171 AC: 2500 AN: 1461226 Hom.: 64 Cov.: 30 AF XY: 0.00147 AC XY: 1068 AN XY: 726928

African (AFR) AF: 0.0628 AC: 2101 AN: 33452

American (AMR) AF: 0.00289 AC: 129 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111688

Other (OTH) AF: 0.00361 AC: 218 AN: 60362

GnomAD4 genome AF: 0.0179 AC: 2727 AN: 152252 Hom.: 81 Cov.: 33 AF XY: 0.0171 AC XY: 1270 AN XY: 74454

African (AFR) AF: 0.0621 AC: 2580 AN: 41514

American (AMR) AF: 0.00686 AC: 105 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00868 Hom.: 30

Bravo AF: 0.0208

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9503924; hg19: chr6-4126380;