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rs1258184

chr10-49752163-G-Achr10-49752163-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_018245.3(OGDHL):c.564C>T(p.Leu188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,613,382 control chromosomes in the GnomAD database, including 193,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 14875 hom., cov: 32)
Exomes 𝑓: 0.48 ( 178488 hom. )

Consequence

OGDHL
NM_018245.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.99
Variant links:
Genes affected
OGDHL (HGNC:25590): (oxoglutarate dehydrogenase L) The protein encoded by this gene is similar to oxoglutarate dehydrogenase (OGDH) of the OGDH complex, which degrades glucose and glutamate. This gene encodes several isoforms, including some that appear to localize to mitochondria. The encoded protein down-regulates the AKT signaling cascade and can suppress the growth of cervical cancer cells. [provided by RefSeq, Dec 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-49752163-G-A is Benign according to our data. Variant chr10-49752163-G-A is described in ClinVar as [Benign]. Clinvar id is 3059593.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.99 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGDHLNM_018245.3 linkuse as main transcriptc.564C>T p.Leu188= synonymous_variant 5/23 ENST00000374103.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGDHLENST00000374103.9 linkuse as main transcriptc.564C>T p.Leu188= synonymous_variant 5/231 NM_018245.3 P1Q9ULD0-1
OGDHLENST00000419399.4 linkuse as main transcriptc.393C>T p.Leu131= synonymous_variant 4/222 Q9ULD0-2
OGDHLENST00000432695.2 linkuse as main transcriptc.-64C>T 5_prime_UTR_variant 3/212 Q9ULD0-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.412
AC:
62596
AN:
151936
Hom.:
14876
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.188
Gnomad AMI
AF:
0.534
Gnomad AMR
AF:
0.486
Gnomad ASJ
AF:
0.343
Gnomad EAS
AF:
0.888
Gnomad SAS
AF:
0.426
Gnomad FIN
AF:
0.510
Gnomad MID
AF:
0.386
Gnomad NFE
AF:
0.481
Gnomad OTH
AF:
0.422
GnomAD3 exomes
AF:
0.489
AC:
122670
AN:
251048
Hom.:
32572
AF XY:
0.483
AC XY:
65599
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.182
Gnomad AMR exome
AF:
0.548
Gnomad ASJ exome
AF:
0.335
Gnomad EAS exome
AF:
0.891
Gnomad SAS exome
AF:
0.413
Gnomad FIN exome
AF:
0.510
Gnomad NFE exome
AF:
0.481
Gnomad OTH exome
AF:
0.463
GnomAD4 exome
AF:
0.485
AC:
708694
AN:
1461328
Hom.:
178488
Cov.:
47
AF XY:
0.481
AC XY:
350030
AN XY:
726986
show subpopulations
Gnomad4 AFR exome
AF:
0.173
Gnomad4 AMR exome
AF:
0.541
Gnomad4 ASJ exome
AF:
0.332
Gnomad4 EAS exome
AF:
0.885
Gnomad4 SAS exome
AF:
0.411
Gnomad4 FIN exome
AF:
0.513
Gnomad4 NFE exome
AF:
0.487
Gnomad4 OTH exome
AF:
0.469
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.412
AC:
62608
AN:
152054
Hom.:
14875
Cov.:
32
AF XY:
0.415
AC XY:
30858
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.188
Gnomad4 AMR
AF:
0.486
Gnomad4 ASJ
AF:
0.343
Gnomad4 EAS
AF:
0.888
Gnomad4 SAS
AF:
0.427
Gnomad4 FIN
AF:
0.510
Gnomad4 NFE
AF:
0.481
Gnomad4 OTH
AF:
0.426
Alfa
AF:
0.451
Hom.:
18826
Bravo
AF:
0.405
Asia WGS
AF:
0.640
AC:
2224
AN:
3478
EpiCase
AF:
0.467
EpiControl
AF:
0.463

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

OGDHL-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 11, 2021This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
2.0
Dann
Benign
0.65

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

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

Other links and lift over

dbSNP: rs1258184; hg19: chr10-50960209; COSMIC: COSV65103994; COSMIC: COSV65103994; API