6-31365722-G-A

Variant names:

• chr6-31365722-G-A
• rs2523545
• ENST00000696559.1:c.-204+21C>T

Variant summary

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

The ENST00000696559.1(HLA-B):​c.-204+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,070 control chromosomes in the GnomAD database, including 36,525 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 0.69 (36525 hom., cov: 31)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 8 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]

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

ENSG00000293281 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000696559.1		c.-204+21C>T		intron	N/A	ENSP00000512717.1
	HLA-B	ENST00000696560.1		c.-204+21C>T		intron	N/A	ENSP00000512718.1
	HLA-B	ENST00000696561.1		c.-300+21C>T		intron	N/A	ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104668 AN: 151952 Hom.: 36482 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.689 AC: 104761 AN: 152070 Hom.: 36525 Cov.: 31 AF XY: 0.700 AC XY: 52020 AN XY: 74348

African (AFR) AF: 0.657 AC: 27243 AN: 41440

American (AMR) AF: 0.725 AC: 11076 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2870 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4762 AN: 5174

South Asian (SAS) AF: 0.830 AC: 4003 AN: 4824

European-Finnish (FIN) AF: 0.765 AC: 8090 AN: 10582

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44359 AN: 67992

Other (OTH) AF: 0.691 AC: 1456 AN: 2106

Alfa AF: 0.693 Hom.: 17311

Bravo AF: 0.679

Asia WGS AF: 0.855 AC: 2976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.3
DANN	Benign	0.44
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs2523545; hg19: chr6-31333499;