rs2523575

Variant names:

• chr6-31361049-C-G
• rs2523575
• ENST00000696690.1:n.3578G>C

Variant summary

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

The ENST00000696690.1(ENSG00000293281):​n.3578G>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 0.203 in 151,678 control chromosomes in the GnomAD database, including 3,478 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 0.20 (3478 hom., cov: 32)
• Consequence: ENSG00000293281 ENST00000696690.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 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.3578G>C		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-B	ENST00000696559.1	c.-203-3368G>C		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-203-3368G>C		intron_variant	Intron 1 of 9			ENSP00000512718.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30810 AN: 151560 Hom.: 3473 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.203 AC: 30837 AN: 151678 Hom.: 3478 Cov.: 32 AF XY: 0.199 AC XY: 14745 AN XY: 74112

African (AFR) AF: 0.151 AC: 6229 AN: 41384

American (AMR) AF: 0.191 AC: 2910 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3464

East Asian (EAS) AF: 0.124 AC: 638 AN: 5128

South Asian (SAS) AF: 0.180 AC: 864 AN: 4806

European-Finnish (FIN) AF: 0.156 AC: 1644 AN: 10522

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17206 AN: 67840

Other (OTH) AF: 0.214 AC: 449 AN: 2100

Alfa AF: 0.225 Hom.: 497

Bravo AF: 0.205

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.59
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs2523575; hg19: chr6-31328826;