6-31356866-G-C

Variant names:

• chr6-31356866-G-C
• rs1050517
• NM_005514.8:c.165C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005514.8(HLA-B):​c.165C>G​(p.Thr55Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,043,632 control chromosomes in the GnomAD database, including 189,939 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 0.36 (6140 hom., cov: 7)
  • Exomes 𝑓: 0.50 (183799 hom.)
• Consequence: HLA-B NM_005514.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 17 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]

ENSG00000271581 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.165C>G	p.Thr55Thr	synonymous_variant	Exon 2 of 8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.165C>G	p.Thr55Thr	synonymous_variant	Exon 2 of 8	6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 20074 AN: 55258 Hom.: 6136 Cov.: 7

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.421 AC: 88536 AN: 210386 AF XY: 0.418

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.504 AC: 498297 AN: 988308 Hom.: 183799 Cov.: 24 AF XY: 0.502 AC XY: 247327 AN XY: 492314

African (AFR) AF: 0.312 AC: 6497 AN: 20838

American (AMR) AF: 0.502 AC: 15445 AN: 30778

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 11899 AN: 20074

East Asian (EAS) AF: 0.499 AC: 12266 AN: 24594

South Asian (SAS) AF: 0.427 AC: 23233 AN: 54388

European-Finnish (FIN) AF: 0.393 AC: 12707 AN: 32374

Middle Eastern (MID) AF: 0.428 AC: 1192 AN: 2788

European-Non Finnish (NFE) AF: 0.518 AC: 394659 AN: 761166

Other (OTH) AF: 0.494 AC: 20399 AN: 41308

GnomAD4 genome AF: 0.363 AC: 20098 AN: 55324 Hom.: 6140 Cov.: 7 AF XY: 0.344 AC XY: 8900 AN XY: 25872

African (AFR) AF: 0.203 AC: 2819 AN: 13894

American (AMR) AF: 0.399 AC: 2102 AN: 5266

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 1177 AN: 1856

East Asian (EAS) AF: 0.487 AC: 587 AN: 1206

South Asian (SAS) AF: 0.271 AC: 292 AN: 1076

European-Finnish (FIN) AF: 0.304 AC: 1103 AN: 3626

Middle Eastern (MID) AF: 0.357 AC: 40 AN: 112

European-Non Finnish (NFE) AF: 0.423 AC: 11584 AN: 27358

Other (OTH) AF: 0.382 AC: 243 AN: 636

Alfa AF: 0.364 Hom.: 1744

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.3
DANN	Benign	0.50
PhyloP100		-0.077
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1050517; hg19: chr6-31324643; COSMIC: COSV69520233; COSMIC: COSV69520233;