Variant rs2257269 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005514.8(HLA-B):c.636C>T(p.His212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 909 hom., cov: 9)

Exomes 𝑓: 0.24 ( 63392 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

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:

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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 (BayesDel_noAF=-0.93).

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.636C>T	p.His212=	synonymous_variant	4/8	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.636C>T	p.His212=	synonymous_variant	4/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

10072

AN:

64482

Hom.:

908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0851

Gnomad FIN

AF:

0.0894

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.400

AC:

100383

AN:

250894

Hom.:

20516

AF XY:

0.394

AC XY:

53412

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.447

Gnomad ASJ exome

AF:

0.490

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.244

AC:

245885

AN:

1006204

Hom.:

63392

Cov.:

AF XY:

0.247

AC XY:

125274

AN XY:

507318

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.416

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.156

AC:

10087

AN:

64572

Hom.:

909

Cov.:

AF XY:

0.147

AC XY:

4522

AN XY:

30772

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0845

Gnomad4 FIN

AF:

0.0894

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.405

Hom.:

5293

Asia WGS

AF:

0.366

AC:

1274

AN:

3478

EpiCase

AF:

0.428

EpiControl

AF:

0.438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.2

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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