6-31356856-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005514.8(HLA-B):​c.175A>C​(p.Arg59Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0011 (14 hom., cov: 9)
  • Exomes 𝑓: 0.0039 (589 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 5 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.221 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	NM_005514.8	MANE Select	c.175A>C	p.Arg59Arg	synonymous	Exon 2 of 8	NP_005505.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.175A>C	p.Arg59Arg	synonymous	Exon 2 of 8	ENSP00000399168.2
	HLA-B	ENST00000696559.1		c.175A>C	p.Arg59Arg	synonymous	Exon 5 of 11	ENSP00000512717.1
	HLA-B	ENST00000696560.1		c.175A>C	p.Arg59Arg	synonymous	Exon 4 of 10	ENSP00000512718.1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 76 AN: 67974 Hom.: 14 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000313

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0474

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

GnomAD2 exomes AF: 0.00247 AC: 560 AN: 226310 AF XY: 0.00245

Gnomad AFR exome AF: 0.000848

Gnomad AMR exome AF: 0.000713

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0269

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.00145

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00392 AC: 4235 AN: 1081684 Hom.: 589 Cov.: 27 AF XY: 0.00396 AC XY: 2133 AN XY: 537972

African (AFR) AF: 0.00290 AC: 67 AN: 23082

American (AMR) AF: 0.00684 AC: 222 AN: 32462

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 25 AN: 21208

East Asian (EAS) AF: 0.0961 AC: 2531 AN: 26332

South Asian (SAS) AF: 0.00606 AC: 347 AN: 57282

European-Finnish (FIN) AF: 0.000560 AC: 20 AN: 35720

Middle Eastern (MID) AF: 0.00326 AC: 10 AN: 3070

European-Non Finnish (NFE) AF: 0.00107 AC: 900 AN: 837778

Other (OTH) AF: 0.00253 AC: 113 AN: 44750

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00113 AC: 77 AN: 68052 Hom.: 14 Cov.: 9 AF XY: 0.00112 AC XY: 36 AN XY: 32194

African (AFR) AF: 0.00 AC: 0 AN: 17206

American (AMR) AF: 0.000313 AC: 2 AN: 6390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2052

East Asian (EAS) AF: 0.0477 AC: 74 AN: 1550

South Asian (SAS) AF: 0.000778 AC: 1 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: 33522

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

Alfa AF: 0.00297 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.49
PhyloP100		-0.22
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1065378; hg19: chr6-31324633;