6-31366162-A-G

Variant names:

• chr6-31366162-A-G
• rs7761068
• ENST00000474381.2:n.851T>C

Variant summary

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

The ENST00000474381.2(HLA-B):​n.851T>C variant causes a non coding transcript exon 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 ENST00000474381.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 11 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]

ENSG00000293281 (HGNC:):

DHFRP2 (HGNC:2863): (dihydrofolate reductase pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DHFRP2		n.31366162A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000474381.2	n.851T>C		non_coding_transcript_exon_variant	Exon 1 of 9	6
HLA-B	ENST00000481849.6	n.851T>C		non_coding_transcript_exon_variant	Exon 1 of 8	6
HLA-B	ENST00000497377.6	n.851T>C		non_coding_transcript_exon_variant	Exon 1 of 9	6

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

African (AFR) AF: 0.579 AC: 23996 AN: 41452

American (AMR) AF: 0.640 AC: 9778 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2618 AN: 3472

East Asian (EAS) AF: 0.738 AC: 3818 AN: 5174

South Asian (SAS) AF: 0.715 AC: 3447 AN: 4822

European-Finnish (FIN) AF: 0.566 AC: 5986 AN: 10568

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29994 AN: 68010

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

Alfa AF: 0.510 Hom.: 6309

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
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs7761068; hg19: chr6-31333939;