rs2596546

Variant names:

• chr6-31361609-A-G
• rs2596546
• ENST00000696690.1:n.3018T>C

Variant summary

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

The ENST00000696690.1(ENSG00000293281):​n.3018T>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 0.376 in 151,864 control chromosomes in the GnomAD database, including 11,112 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 0.38 (11112 hom., cov: 30)
• Consequence: ENSG00000293281 ENST00000696690.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 10 publications found

Genes affected

ENSG00000293281 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 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
ENSG00000293281	ENST00000696690.1	n.3018T>C		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-B	ENST00000696559.1	c.-203-3928T>C		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-203-3928T>C		intron_variant	Intron 1 of 9			ENSP00000512718.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56959 AN: 151746 Hom.: 11086 Cov.: 30

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.376 AC: 57026 AN: 151864 Hom.: 11112 Cov.: 30 AF XY: 0.374 AC XY: 27732 AN XY: 74212

African (AFR) AF: 0.446 AC: 18450 AN: 41376

American (AMR) AF: 0.388 AC: 5933 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2066 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1819 AN: 5158

South Asian (SAS) AF: 0.258 AC: 1242 AN: 4812

European-Finnish (FIN) AF: 0.371 AC: 3919 AN: 10560

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22253 AN: 67918

Other (OTH) AF: 0.387 AC: 811 AN: 2096

Alfa AF: 0.356 Hom.: 1186

Bravo AF: 0.384

Asia WGS AF: 0.273 AC: 951 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	9.9
DANN	Benign	0.29
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs2596546; hg19: chr6-31329386;