Variant 6-31354590-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005514.8(HLA-B):c.1045+43A>C 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 0.023 ( 33 hom., cov: 12)

Exomes 𝑓: 0.048 ( 2663 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0232 (2161/93004) while in subpopulation SAS AF= 0.0474 (92/1942). AF 95% confidence interval is 0.0396. There are 33 homozygotes in gnomad4. There are 985 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.1045+43A>C		intron_variant		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.1045+43A>C		intron_variant			NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

2158

AN:

92946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00823

Gnomad AMI

AF:

0.0178

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0154

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.0469

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0364

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0160

GnomAD3 exomes

AF:

0.0773

AC:

19444

AN:

251434

Hom.:

915

AF XY:

0.0785

AC XY:

10667

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0290

Gnomad EAS exome

AF:

0.0685

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0768

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0482

AC:

64680

AN:

1342570

Hom.:

2663

Cov.:

AF XY:

0.0508

AC XY:

33979

AN XY:

668734

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.0970

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.0793

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0891

Gnomad4 NFE exome

AF:

0.0405

Gnomad4 OTH exome

AF:

0.0460

GnomAD4 genome

AF:

0.0232

AC:

2161

AN:

93004

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

985

AN XY:

43676

show subpopulations

Gnomad4 AFR

AF:

0.00816

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.0154

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.0474

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0159

Alfa

AF:

0.0524

Hom.:

265

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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