rs2523544

Positions:

• chr6-31365785-G-A
• chr6-31365785-G-T

Variant summary

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

The ENST00000696690.1(ENSG00000293281):​n.1570C>T 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 0.15 in 152,154 control chromosomes in the GnomAD database, including 2,085 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 0.15 (2085 hom., cov: 33)
• Consequence: ENST00000696690.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000696690.1	n.1570C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22752 AN: 152036 Hom.: 2089 Cov.: 33

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.150 AC: 22752 AN: 152154 Hom.: 2085 Cov.: 33 AF XY: 0.145 AC XY: 10790 AN XY: 74386

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.0844

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.115

Alfa AF: 0.186 Hom.: 3872

Bravo AF: 0.137

Asia WGS AF: 0.109 AC: 380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523544; hg19: chr6-31333562;