Variant 8-144051721-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000618853.5(OPLAH):c.3720+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 0.00127 in 1,592,084 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 8 hom., cov: 30)

Exomes 𝑓: 0.00074 ( 10 hom. )

Consequence

OPLAH
ENST00000618853.5 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.74

Variant links:

Genes affected

OPLAH (HGNC:8149): (5-oxoprolinase, ATP-hydrolysing) The protein encoded by this gene acts as a homodimer, using ATP hydrolysis to catalyze the conversion of 5-oxo-L-proline to L-glutamate. Defects in this gene are a cause of 5-oxoprolinase deficiency (OPLAHD). [provided by RefSeq, Jun 2012]

OPLAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 8-144051721-G-A is Benign according to our data. Variant chr8-144051721-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 714648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (955/152138) while in subpopulation AFR AF= 0.0218 (903/41500). AF 95% confidence interval is 0.0206. There are 8 homozygotes in gnomad4. There are 423 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPLAH	NM_017570.5 linkuse as main transcript	c.3720+8C>T		splice_region_variant, intron_variant		ENST00000618853.5	NP_060040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5 linkuse as main transcript	c.3720+8C>T		splice_region_variant, intron_variant		1	NM_017570.5	ENSP00000480476	P1

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

955

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00179

AC:

384

AN:

214998

Hom.:

AF XY:

0.00137

AC XY:

162

AN XY:

118226

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000362

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.000922

GnomAD4 exome

AF:

0.000737

AC:

1061

AN:

1439946

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

457

AN XY:

715524

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000761

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00628

AC:

955

AN:

152138

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

423

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00725

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

5-Oxoprolinase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 15, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.045

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

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