chr6-31366162-A-G

Position:

• chr6-31366162-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696560.1(HLA-B):​c.-623T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,102 control chromosomes in the GnomAD database, including 22,761 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 0.54 (22761 hom., cov: 33)
• Consequence: HLA-B ENST00000696560.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFRP2		n.31366162A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696560.1	c.-623T>C		5_prime_UTR_variant	1/10			ENSP00000512718.1
HLA-B	ENST00000696562.1	c.-555T>C		5_prime_UTR_variant	1/9			ENSP00000512720.1
HLA-B	ENST00000696559.1	c.-252-371T>C		intron_variant				ENSP00000512717.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81436 AN: 151984 Hom.: 22723 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.536 AC: 81526 AN: 152102 Hom.: 22761 Cov.: 33 AF XY: 0.551 AC XY: 40942 AN XY: 74354

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.571

Alfa AF: 0.507 Hom.: 3456

Bravo AF: 0.539

Asia WGS AF: 0.704 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.0
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7761068; hg19: chr6-31333939;