6-31357052-G-T

Position:

• chr6-31357052-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005514.8(HLA-B):​c.73+34C>A variant causes a intron 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 0.00080 (0 hom., cov: 3)
  • Exomes 𝑓: 0.0029 (81 hom.)
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAd4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.73+34C>A		intron_variant		ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.73+34C>A		intron_variant			NM_005514.8	P1
	ENST00000603274.1	n.406G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.000816 AC: 39 AN: 47782 Hom.: 0 Cov.: 3

Gnomad AFR AF: 0.000922

Gnomad AMI AF: 0.00352

Gnomad AMR AF: 0.000226

Gnomad ASJ AF: 0.000635

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00587

Gnomad FIN AF: 0.000316

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000830

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0148 AC: 2222 AN: 149916 Hom.: 105 AF XY: 0.0156 AC XY: 1284 AN XY: 82384

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.00853

Gnomad ASJ exome AF: 0.0240

Gnomad EAS exome AF: 0.000887

Gnomad SAS exome AF: 0.0294

Gnomad FIN exome AF: 0.00280

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.00292 AC: 2223 AN: 761106 Hom.: 81 Cov.: 16 AF XY: 0.00336 AC XY: 1273 AN XY: 378514

Gnomad4 AFR exome AF: 0.00473

Gnomad4 AMR exome AF: 0.00261

Gnomad4 ASJ exome AF: 0.00543

Gnomad4 EAS exome AF: 0.000242

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00211

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.000795 AC: 38 AN: 47796 Hom.: 0 Cov.: 3 AF XY: 0.000758 AC XY: 17 AN XY: 22432

Gnomad4 AFR AF: 0.000828

Gnomad4 AMR AF: 0.000226

Gnomad4 ASJ AF: 0.000635

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00585

Gnomad4 FIN AF: 0.000316

Gnomad4 NFE AF: 0.000830

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0118 Hom.: 943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9266196; hg19: chr6-31324829;