10-133362754-G-A

Position:

• chr10-133362754-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004092.4(ECHS1):​c.*114C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,218,806 control chromosomes in the GnomAD database, including 1,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (677 hom., cov: 33)
  • Exomes 𝑓: 0.0093 (486 hom.)
• Consequence: ECHS1 NM_004092.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110

Genes affected

ECHS1 (HGNC:3151): (enoyl-CoA hydratase, short chain 1) The protein encoded by this gene functions in the second step of the mitochondrial fatty acid beta-oxidation pathway. It catalyzes the hydration of 2-trans-enoyl-coenzyme A (CoA) intermediates to L-3-hydroxyacyl-CoAs. The gene product is a member of the hydratase/isomerase superfamily. It localizes to the mitochondrial matrix. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 10-133362754-G-A is Benign according to our data. Variant chr10-133362754-G-A is described in ClinVar as [Benign]. Clinvar id is 1258110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECHS1	NM_004092.4	c.*114C>T		3_prime_UTR_variant	8/8	ENST00000368547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECHS1	ENST00000368547.4	c.*114C>T		3_prime_UTR_variant	8/8	1	NM_004092.4	P1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8181 AN: 152176 Hom.: 673 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.00928 AC: 9899 AN: 1066512 Hom.: 486 Cov.: 14 AF XY: 0.00843 AC XY: 4604 AN XY: 546430

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.0312

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.00532

Gnomad4 FIN exome AF: 0.00504

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.0538 AC: 8201 AN: 152294 Hom.: 677 Cov.: 33 AF XY: 0.0522 AC XY: 3886 AN XY: 74466

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0160 Hom.: 144

Bravo AF: 0.0605

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.53

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: rs1050040; hg19: chr10-135176258; COSMIC: COSV53369799; COSMIC: COSV53369799;