rs1268722

Positions:

• chr10-49743164-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018245.3(OGDHL):​c.1862-186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,248 control chromosomes in the GnomAD database, including 13,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (13542 hom., cov: 35)
• Consequence: OGDHL NM_018245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGDHL	NM_018245.3	c.1862-186C>T		intron_variant		ENST00000374103.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGDHL	ENST00000374103.9	c.1862-186C>T		intron_variant		1	NM_018245.3	P1
OGDHL	ENST00000419399.4	c.1691-186C>T		intron_variant		2
OGDHL	ENST00000432695.2	c.1235-186C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57577 AN: 152132 Hom.: 13543 Cov.: 35

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.378 AC: 57580 AN: 152248 Hom.: 13542 Cov.: 35 AF XY: 0.383 AC XY: 28472 AN XY: 74436

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.400

Alfa AF: 0.428 Hom.: 6531

Bravo AF: 0.370

Asia WGS AF: 0.617 AC: 2145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1268722; hg19: chr10-50951210;