Variant 6-31356418-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005514.8(HLA-B):c.368A>C(p.Tyr123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y123F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 5)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.869

Variant links:

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

HLA-B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016054064).

BP6

Variant 6-31356418-T-G is Benign according to our data. Variant chr6-31356418-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025032.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.368A>C	p.Tyr123Ser	missense_variant	3/8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.368A>C	p.Tyr123Ser	missense_variant	3/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.000279

AC:

AN:

46618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00154

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000406

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00378

AC:

759

AN:

200890

Hom.:

AF XY:

0.00382

AC XY:

418

AN XY:

109542

show subpopulations

Gnomad AFR exome

AF:

0.00188

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00338

Gnomad SAS exome

AF:

0.00945

Gnomad FIN exome

AF:

0.000689

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00503

GnomAD4 exome

AF:

0.000995

AC:

875

AN:

879152

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

489

AN XY:

436992

show subpopulations

Gnomad4 AFR exome

AF:

0.000262

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00122

Gnomad4 SAS exome

AF:

0.00425

Gnomad4 FIN exome

AF:

0.000387

Gnomad4 NFE exome

AF:

0.000771

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.000279

AC:

AN:

46638

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

AN XY:

22042

show subpopulations

Gnomad4 AFR

AF:

0.0000845

Gnomad4 AMR

AF:

0.000282

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00155

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000406

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00471

Hom.:

ExAC

AF:

0.00156

AC:

177

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

HLA-B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.5

DANN

Benign

0.47

DEOGEN2

Benign

0.024

T;.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.097

T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-5.3

D;.;D

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;.;D

Sift4G

Benign

0.22

T;.;T

Polyphen

0.0050

B;.;.

Vest4

0.26

MVP

0.085

MPC

0.77

ClinPred

0.077

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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