6-31356856-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_005514.8(HLA-B):c.175A>C(p.Arg59=) 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.221 with no splicing effect.
• BS2: High AC in GnomAdExome at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.175A>C	p.Arg59=	synonymous_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.175A>C	p.Arg59=	synonymous_variant	2/8		NM_005514.8	P1
	ENST00000603274.1	n.210T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 76 AN: 67974 Hom.: 14 Cov.: 9 FAILED QC

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

GnomAD3 exomes AF: 0.00247 AC: 560 AN: 226310 Hom.: 44 AF XY: 0.00245 AC XY: 302 AN XY: 123206

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 SAS exome AF: 0.00141

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

Gnomad4 AFR exome AF: 0.00290

Gnomad4 AMR exome AF: 0.00684

Gnomad4 ASJ exome AF: 0.00118

Gnomad4 EAS exome AF: 0.0961

Gnomad4 SAS exome AF: 0.00606

Gnomad4 FIN exome AF: 0.000560

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.00253

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000313

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.000778

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00297 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	13
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1065378; hg19: chr6-31324633;