rs2523608

Variant names:

• chr6-31354782-G-A
• rs2523608
• NM_005514.8:c.1013-117C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31354782-G-A
• chr6-31354782-G-C
• chr6-31354782-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005514.8(HLA-B):​c.1013-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.19 (1019 hom., cov: 7)
  • Exomes 𝑓: 0.44 (47168 hom.)
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 78 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]

ENSG00000298396 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.1013-117C>T		intron_variant	Intron 5 of 7	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.1013-117C>T		intron_variant	Intron 5 of 7	6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 8670 AN: 46832 Hom.: 1013 Cov.: 7

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.442 AC: 160943 AN: 364272 Hom.: 47168 Cov.: 6 AF XY: 0.459 AC XY: 88875 AN XY: 193654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.529 AC: 5284 AN: 9998

American (AMR) AF: 0.520 AC: 11629 AN: 22362

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 4402 AN: 10852

East Asian (EAS) AF: 0.262 AC: 3705 AN: 14118

South Asian (SAS) AF: 0.689 AC: 27806 AN: 40342

European-Finnish (FIN) AF: 0.319 AC: 6451 AN: 20204

Middle Eastern (MID) AF: 0.606 AC: 698 AN: 1152

European-Non Finnish (NFE) AF: 0.410 AC: 93217 AN: 227572

Other (OTH) AF: 0.439 AC: 7751 AN: 17672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.185 AC: 8684 AN: 46858 Hom.: 1019 Cov.: 7 AF XY: 0.177 AC XY: 3922 AN XY: 22196

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.189 AC: 1834 AN: 9684

American (AMR) AF: 0.171 AC: 660 AN: 3852

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 290 AN: 1508

East Asian (EAS) AF: 0.110 AC: 237 AN: 2154

South Asian (SAS) AF: 0.195 AC: 161 AN: 826

European-Finnish (FIN) AF: 0.108 AC: 353 AN: 3258

Middle Eastern (MID) AF: 0.237 AC: 18 AN: 76

European-Non Finnish (NFE) AF: 0.201 AC: 4941 AN: 24598

Other (OTH) AF: 0.164 AC: 86 AN: 524

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.600 Hom.: 108600

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.71
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2523608; hg19: chr6-31322559;