Variant 15-51947361-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_138792.4(LEO1):c.1827C>T(p.Asp609=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0037 in 1,611,998 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 166 hom. )

Consequence

LEO1
NM_138792.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

LEO1 (HGNC:30401): (LEO1 homolog, Paf1/RNA polymerase II complex component) LEO1, parafibromin (CDC73; MIM 607393), CTR9 (MIM 609366), and PAF1 (MIM 610506) form the PAF protein complex that associates with the RNA polymerase II subunit POLR2A (MIM 180660) and with a histone methyltransferase complex (Rozenblatt-Rosen et al., 2005 [PubMed 15632063]).[supplied by OMIM, Mar 2008]

LEO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 15-51947361-G-A is Benign according to our data. Variant chr15-51947361-G-A is described in ClinVar as [Benign]. Clinvar id is 3044065.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00209 (318/151950) while in subpopulation SAS AF= 0.0429 (206/4804). AF 95% confidence interval is 0.0381. There are 6 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEO1	NM_138792.4 linkuse as main transcript	c.1827C>T	p.Asp609=	synonymous_variant	11/12	ENST00000299601.10	NP_620147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEO1	ENST00000299601.10 linkuse as main transcript	c.1827C>T	p.Asp609=	synonymous_variant	11/12	1	NM_138792.4	ENSP00000299601	P1	Q8WVC0-1
LEO1	ENST00000315141.5 linkuse as main transcript	c.1647C>T	p.Asp549=	synonymous_variant	9/10	2		ENSP00000314610		Q8WVC0-2

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

317

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0426

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0129

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00713

AC:

1790

AN:

251112

Hom.:

AF XY:

0.00939

AC XY:

1275

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00844

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0501

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00387

AC:

5654

AN:

1460048

Hom.:

166

Cov.:

AF XY:

0.00540

AC XY:

3923

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00812

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0507

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000597

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

151950

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

214

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0429

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00110

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LEO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This 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

-0.37

CADD

Benign

DANN

Benign

0.79

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