Variant 18-677452-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017512.7(ENOSF1):c.1049-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,610,548 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 39 hom. )

Consequence

ENOSF1
NM_017512.7 splice_region, intron

Scores

Splicing: ADA: 0.00008796

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.220

Variant links:

Genes affected

ENOSF1 (HGNC:30365): (enolase superfamily member 1) This gene can encode a mitochondrial enzyme that is thought to convert L-fuconate to 2-keto-3-deoxy-L-fuconate. This locus was originally identified as the source of antisense RNAs of the adjacent thymidylate synthase gene. Splice variants at this locus may contain an alternate 3' exon that is complementary to the 3'UTR and terminal intron of the thymidylate synthase (TS) RNA and may downregulate TS expression. [provided by RefSeq, Aug 2017]

ENOSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 18-677452-G-A is Benign according to our data. Variant chr18-677452-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7 linkuse as main transcript	c.1049-8C>T		splice_region_variant, intron_variant		ENST00000647584.2	NP_059982.2	Q7L5Y1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2 linkuse as main transcript	c.1049-8C>T		splice_region_variant, intron_variant			NM_017512.7	ENSP00000497230.2		Q7L5Y1-1

Frequencies

GnomAD3 genomes

AF:

0.00422

AC:

643

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00444

AC:

1098

AN:

247046

Hom.:

AF XY:

0.00449

AC XY:

600

AN XY:

133702

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.00308

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00508

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00666

Gnomad OTH exome

AF:

0.00531

GnomAD4 exome

AF:

0.00624

AC:

9103

AN:

1458236

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

4475

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.000934

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00462

Gnomad4 FIN exome

AF:

0.00204

Gnomad4 NFE exome

AF:

0.00720

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.00422

AC:

643

AN:

152312

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

270

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00651

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00459

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ENOSF1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.1

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over