10-133370917-C-G

Position:

• chr10-133370917-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000368547.4(ECHS1):​c.89-160G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,184 control chromosomes in the GnomAD database, including 60,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.89 (60482 hom., cov: 32)
• Consequence: ECHS1 ENST00000368547.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0340

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-133370917-C-G is Benign according to our data. Variant chr10-133370917-C-G is described in ClinVar as [Benign]. Clinvar id is 683758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECHS1	NM_004092.4	c.89-160G>C		intron_variant		ENST00000368547.4	NP_004083.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECHS1	ENST00000368547.4	c.89-160G>C		intron_variant		1	NM_004092.4	ENSP00000357535	P1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134606 AN: 152066 Hom.: 60454 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.885 AC: 134683 AN: 152184 Hom.: 60482 Cov.: 32 AF XY: 0.889 AC XY: 66159 AN XY: 74424

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.911

Alfa AF: 0.914 Hom.: 3166

Bravo AF: 0.873

Asia WGS AF: 0.965 AC: 3355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.99
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7894051; hg19: chr10-135184421;