chr6-31359924-T-G

Variant names:

• chr6-31359924-T-G
• rs9378249
• ENST00000696559.1:c.-203-2243A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696559.1(HLA-B):​c.-203-2243A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,280 control chromosomes in the GnomAD database, including 298 homozygotes. 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 0.052 (298 hom., cov: 34)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 28 publications found

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]

ENSG00000298426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696559.1	c.-203-2243A>C		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-203-2243A>C		intron_variant	Intron 1 of 9			ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-203-2243A>C		intron_variant	Intron 3 of 11			ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7871 AN: 152162 Hom.: 298 Cov.: 34

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0517 AC: 7868 AN: 152280 Hom.: 298 Cov.: 34 AF XY: 0.0545 AC XY: 4056 AN XY: 74466

African (AFR) AF: 0.00964 AC: 401 AN: 41580

American (AMR) AF: 0.0409 AC: 625 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3466

East Asian (EAS) AF: 0.180 AC: 933 AN: 5170

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4832

European-Finnish (FIN) AF: 0.121 AC: 1282 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0640 AC: 4352 AN: 68006

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0562 Hom.: 23

Bravo AF: 0.0462

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.9
DANN	Benign	0.60
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9378249; hg19: chr6-31327701;