Genetic Variant HLA-B:p.Gly107Arg (chr6-31356712-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005514.8(HLA-B):c.319G>C(p.Gly107Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0054 ( 0 hom., cov: 3)

Exomes 𝑓: 0.016 ( 542 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

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:

ENSG00000271581 (HGNC:):

ENSG00000271581 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022532344).

BS2

High AC in GnomAd4 at 233 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.319G>C	p.Gly107Arg	missense_variant	Exon 2 of 8	ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 link	c.319G>C	p.Gly107Arg	missense_variant	Exon 2 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

232

AN:

43450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00284

Gnomad AMI

AF:

0.0227

Gnomad AMR

AF:

0.00627

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00607

Gnomad SAS

AF:

0.00718

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.0294

Gnomad NFE

AF:

0.00577

Gnomad OTH

AF:

0.00577

GnomAD3 exomes

AF:

0.0573

AC:

8561

AN:

149466

Hom.:

635

AF XY:

0.0604

AC XY:

4791

AN XY:

79364

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0352

Gnomad EAS exome

AF:

0.0491

Gnomad SAS exome

AF:

0.0726

Gnomad FIN exome

AF:

0.0916

Gnomad NFE exome

AF:

0.0636

Gnomad OTH exome

AF:

0.0571

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0156

AC:

16753

AN:

1071146

Hom.:

542

Cov.:

AF XY:

0.0159

AC XY:

8435

AN XY:

530846

show subpopulations

Gnomad4 AFR exome

AF:

0.00486

Gnomad4 AMR exome

AF:

0.00614

Gnomad4 ASJ exome

AF:

0.00777

Gnomad4 EAS exome

AF:

0.0117

Gnomad4 SAS exome

AF:

0.0246

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.00536

AC:

233

AN:

43492

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

112

AN XY:

20946

show subpopulations

Gnomad4 AFR

AF:

0.00295

Gnomad4 AMR

AF:

0.00623

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00610

Gnomad4 SAS

AF:

0.00720

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00577

Gnomad4 OTH

AF:

0.00564

ESP6500AA

AF:

0.0444

AC:

189

ESP6500EA

AF:

0.0468

AC:

392

ExAC

AF:

0.0590

AC:

6533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.5

DANN

Benign

0.39

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.025

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-0.98

PROVEAN

Uncertain

-3.4

D;.;D

REVEL

Benign

0.24

Sift

Benign

0.26

T;.;D

Sift4G

Benign

0.28

T;.;T

Polyphen

0.0040

B;.;.

Vest4

0.079

MPC

0.29

ClinPred

0.0083

GERP RS

-0.99

Varity_R

0.38

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over