NM_005514.8:c.*196C>T

Variant names:

• chr6-31354105-G-A
• rs2769
• NM_005514.8:c.*196C>T

Variant summary

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

The NM_005514.8(HLA-B):​c.*196C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 452,790 control chromosomes in the GnomAD database, including 1,309 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 0.099 (630 hom., cov: 31)
  • Exomes 𝑓: 0.071 (679 hom.)
• Consequence: HLA-B NM_005514.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• Publications: 20 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]

ENSG00000298426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.*196C>T		3_prime_UTR_variant	Exon 8 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.*196C>T		3_prime_UTR_variant	Exon 8 of 8	6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 14981 AN: 151080 Hom.: 630 Cov.: 31

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0707 AC: 21331 AN: 301592 Hom.: 679 Cov.: 0 AF XY: 0.0671 AC XY: 10662 AN XY: 159008

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

African (AFR) AF: 0.0431 AC: 408 AN: 9462

American (AMR) AF: 0.0537 AC: 752 AN: 14000

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 383 AN: 9770

East Asian (EAS) AF: 0.0460 AC: 933 AN: 20266

South Asian (SAS) AF: 0.0389 AC: 1573 AN: 40412

European-Finnish (FIN) AF: 0.0413 AC: 1059 AN: 25668

Middle Eastern (MID) AF: 0.0360 AC: 92 AN: 2554

European-Non Finnish (NFE) AF: 0.0909 AC: 14779 AN: 162556

Other (OTH) AF: 0.0800 AC: 1352 AN: 16904

⚠️ 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: 0.0991 AC: 14984 AN: 151198 Hom.: 630 Cov.: 31 AF XY: 0.0945 AC XY: 6988 AN XY: 73936

African (AFR) AF: 0.0639 AC: 2641 AN: 41356

American (AMR) AF: 0.105 AC: 1592 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 225 AN: 3454

East Asian (EAS) AF: 0.0256 AC: 132 AN: 5166

South Asian (SAS) AF: 0.0824 AC: 395 AN: 4792

European-Finnish (FIN) AF: 0.0591 AC: 623 AN: 10548

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9024 AN: 67428

Other (OTH) AF: 0.0980 AC: 206 AN: 2102

Alfa AF: 0.114 Hom.: 454

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.39
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2769; hg19: chr6-31321882;