chr6-31356856-T-A

Variant names:

• chr6-31356856-T-A
• rs1065378
• NM_005514.8:c.175A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005514.8(HLA-B):​c.175A>T​(p.Arg59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 9)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33180374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005514.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	NM_005514.8	MANE Select	c.175A>T	p.Arg59Trp	missense	Exon 2 of 8	NP_005505.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.175A>T	p.Arg59Trp	missense	Exon 2 of 8	ENSP00000399168.2	P01889
	HLA-B	ENST00000696559.1		c.175A>T	p.Arg59Trp	missense	Exon 5 of 11	ENSP00000512717.1	P01889
	HLA-B	ENST00000696560.1		c.175A>T	p.Arg59Trp	missense	Exon 4 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 67996 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1089908 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 542270

African (AFR) AF: 0.00 AC: 0 AN: 23304

American (AMR) AF: 0.00 AC: 0 AN: 33342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21402

East Asian (EAS) AF: 0.00 AC: 0 AN: 26588

South Asian (SAS) AF: 0.00 AC: 0 AN: 58780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842474

Other (OTH) AF: 0.00 AC: 0 AN: 45066

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 68074 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 32206

African (AFR) AF: 0.00 AC: 0 AN: 17216

American (AMR) AF: 0.00 AC: 0 AN: 6390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2054

East Asian (EAS) AF: 0.00 AC: 0 AN: 1558

South Asian (SAS) AF: 0.00 AC: 0 AN: 1286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33524

Other (OTH) AF: 0.00 AC: 0 AN: 816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.22
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.012	D
Polyphen		0.0080	B
Vest4		0.29
MutPred		0.63		Loss of disorder (P = 0.0028)
MVP		0.23
MPC		0.23
ClinPred		0.42	T
GERP RS		1.2
PromoterAI		0.084	Neutral
Varity_R		0.28
gMVP		0.29
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -11

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

Other links and lift over

dbSNP: rs1065378; hg19: chr6-31324633;