10-133362587-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.*281C>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 0.798 in 493,812 control chromosomes in the GnomAD database, including 162,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (42776 hom., cov: 32)
  • Exomes 𝑓: 0.83 (119811 hom.)
• Consequence: ECHS1 NM_004092.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

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=-0.94).
• BP6: Variant 10-133362587-G-A is Benign according to our data. Variant chr10-133362587-G-A is described in ClinVar as [Benign]. Clinvar id is 1265360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECHS1	NM_004092.4	c.*281C>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.*281C>T		3_prime_UTR_variant	8/8	1	NM_004092.4	P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109505 AN: 151878 Hom.: 42759 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.833 AC: 284620 AN: 341816 Hom.: 119811 Cov.: 2 AF XY: 0.832 AC XY: 149330 AN XY: 179520

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.792

Gnomad4 EAS exome AF: 0.960

Gnomad4 SAS exome AF: 0.812

Gnomad4 FIN exome AF: 0.903

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.721 AC: 109544 AN: 151996 Hom.: 42776 Cov.: 32 AF XY: 0.728 AC XY: 54105 AN XY: 74284

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.751

Alfa AF: 0.813 Hom.: 46346

Bravo AF: 0.700

Asia WGS AF: 0.859 AC: 2986 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 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.22
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4604; hg19: chr10-135176091;