Variant 19-54452692-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_052925.4(LENG8):c.255G>C(p.Gln85His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,614,146 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 8 hom. )

Consequence

LENG8
NM_052925.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

LENG8 (HGNC:15500): (leukocyte receptor cluster member 8) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LENG8 links:

LENG8 (HGNC:):

LENG8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00676924).

BP6

Variant 19-54452692-G-C is Benign according to our data. Variant chr19-54452692-G-C is described in ClinVar as [Benign]. Clinvar id is 3049713.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000801 (122/152338) while in subpopulation EAS AF= 0.0182 (94/5178). AF 95% confidence interval is 0.0152. There are 0 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LENG8	NM_052925.4 linkuse as main transcript	c.255G>C	p.Gln85His	missense_variant	4/16	ENST00000326764.10	NP_443157.1	Q96PV6-2A0A024R4R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LENG8	ENST00000326764.10 linkuse as main transcript	c.255G>C	p.Gln85His	missense_variant	4/16	1	NM_052925.4	ENSP00000318374.5		Q96PV6-2

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00150

AC:

376

AN:

251428

Hom.:

AF XY:

0.00136

AC XY:

185

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.0185

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000691

AC:

1010

AN:

1461808

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

475

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0205

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152338

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000284

Hom.:

Bravo

AF:

0.000778

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00141

AC:

171

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LENG8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 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

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

.;T;.;.;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

.;.;T;D;T;.;T

MetaRNN

Benign

0.0068

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.9

.;N;D;.;D;D;.

REVEL

Benign

0.14

Sift

Uncertain

0.026

.;D;D;.;D;D;.

Sift4G

Benign

0.13

T;T;D;T;D;D;D

Vest4

0.41

MutPred

0.62

Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);.;Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);

MVP

0.26

MPC

0.32

ClinPred

0.026

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.16

gMVP

0.94

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