rs2523545

Positions:

• chr6-31365722-G-A
• chr6-31365722-G-C
• chr6-31365722-G-T

Variant summary

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

The ENST00000696690.1(ENSG00000293281):​n.1612+21C>T variant causes a intron, non coding transcript 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: ENST00000696690.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

Genes affected

(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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000696690.1	n.1612+21C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.691

Alfa AF: 0.690 Hom.: 9581

Bravo AF: 0.679

Asia WGS AF: 0.855 AC: 2976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523545; hg19: chr6-31333499;