Variant chr6-31357052-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005514.8(HLA-B):c.73+34C>G variant causes a intron 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 0.056 ( 327 hom., cov: 3)

Exomes 𝑓: 0.12 ( 39799 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.73+34C>G		intron_variant		ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 link	c.73+34C>G		intron_variant		6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

2350

AN:

42020

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.0444

Gnomad AMR

AF:

0.0489

Gnomad ASJ

AF:

0.0474

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0698

GnomAD3 exomes

AF:

0.637

AC:

95424

AN:

149916

Hom.:

39061

AF XY:

0.645

AC XY:

53175

AN XY:

82384

show subpopulations

Gnomad AFR exome

AF:

0.693

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.533

Gnomad EAS exome

AF:

0.886

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.122

AC:

87109

AN:

714552

Hom.:

39799

Cov.:

AF XY:

0.134

AC XY:

47778

AN XY:

355824

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.0813

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.0558

AC:

2347

AN:

42038

Hom.:

327

Cov.:

AF XY:

0.0510

AC XY:

1024

AN XY:

20060

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.0489

Gnomad4 ASJ

AF:

0.0474

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0595

Gnomad4 OTH

AF:

0.0766

Alfa

AF:

0.329

Hom.:

943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

6.5

DANN

Benign

0.46

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