Variant 1-160799900-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002348.4(LY9):c.272G>A(p.Arg91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,614,114 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R91C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 26 hom. )

Consequence

LY9
NM_002348.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -6.85

Variant links:

Genes affected

LY9 (HGNC:6730): (lymphocyte antigen 9) LY9 belongs to the SLAM family of immunomodulatory receptors (see SLAMF1; MIM 603492) and interacts with the adaptor molecule SAP (SH2D1A; MIM 300490) (Graham et al., 2006 [PubMed 16365421]).[supplied by OMIM, Mar 2008]

LY9 links:

LY9 (HGNC:):

LY9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038803518).

BP6

Variant 1-160799900-G-A is Benign according to our data. Variant chr1-160799900-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038300.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY9	NM_002348.4 linkuse as main transcript	c.272G>A	p.Arg91His	missense_variant	2/10	ENST00000263285.11	NP_002339.2	Q9HBG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY9	ENST00000263285.11 linkuse as main transcript	c.272G>A	p.Arg91His	missense_variant	2/10	1	NM_002348.4	ENSP00000263285.5		Q9HBG7-1

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00258

AC:

649

AN:

251486

Hom.:

AF XY:

0.00248

AC XY:

337

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000924

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00466

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00402

AC:

5880

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

2761

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.00490

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.00281

AC:

428

AN:

152244

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00255

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00265

AC:

322

EpiCase

AF:

0.00403

EpiControl

AF:

0.00415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LY9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2024

This variant is classified as likely 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

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0030

DANN

Benign

0.47

DEOGEN2

Benign

0.054

.;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.43

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.46

.;.;N;N

REVEL

Benign

0.020

Sift

Benign

0.59

.;.;T;T

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.0010

B;.;B;.

Vest4

0.079

MVP

0.41

MPC

0.072

ClinPred

0.010

GERP RS

-8.1

Varity_R

0.016

gMVP

0.18

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