Variant 6-6625004-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004271.4(LY86):c.215T>G(p.Ile72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,456,932 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

LY86
NM_004271.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

LY86 (HGNC:16837): (lymphocyte antigen 86) Acts upstream of or within positive regulation of lipopolysaccharide-mediated signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LY86 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15228179).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY86	NM_004271.4 linkuse as main transcript	c.215T>G	p.Ile72Ser	missense_variant	2/5	ENST00000230568.5	NP_004262.1	O95711

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY86	ENST00000230568.5 linkuse as main transcript	c.215T>G	p.Ile72Ser	missense_variant	2/5	1	NM_004271.4	ENSP00000230568.3		O95711
LY86	ENST00000379953.6 linkuse as main transcript	c.215T>G	p.Ile72Ser	missense_variant	3/6	5		ENSP00000369286.1		O95711

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000555

AC:

119

AN:

214380

Hom.:

AF XY:

0.000597

AC XY:

AN XY:

115568

show subpopulations

Gnomad AFR exome

AF:

0.0000706

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000265

AC:

346

AN:

1304580

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

184

AN XY:

653980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000754

Gnomad4 ASJ exome

AF:

0.0000405

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000981

Gnomad4 FIN exome

AF:

0.000925

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000492

GnomAD4 genome

AF:

0.000269

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000768

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.215T>G (p.I72S) alteration is located in exon 2 (coding exon 2) of the LY86 gene. This alteration results from a T to G substitution at nucleotide position 215, causing the isoleucine (I) at amino acid position 72 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;D

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.96

P;P

Vest4

0.60

MVP

0.60

MPC

0.056

ClinPred

0.052

GERP RS

4.1

Varity_R

0.52

gMVP

0.75

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