rs17881210

chr6-31356671-G-Achr6-31356671-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005514.8(HLA-B):c.343+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 89,102 control chromosomes in the GnomAD database, including 32 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 0.013 (32 hom., cov: 12)
  • Exomes 𝑓: 0.0086 (291 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (1188/89102) while in subpopulation AFR AF= 0.0295 (684/23150). AF 95% confidence interval is 0.0277. There are 32 homozygotes in gnomad4. There are 585 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.343+17C>T		intron_variant		ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.343+17C>T		intron_variant			NM_005514.8	P1
	ENST00000603274.1	n.25G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 1190 AN: 89026 Hom.: 32 Cov.: 12

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.00405

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.00543

Gnomad NFE AF: 0.00707

Gnomad OTH AF: 0.0133

GnomAD3 exomes AF: 0.0833 AC: 19872 AN: 238624 Hom.: 1207 AF XY: 0.0785 AC XY: 10194 AN XY: 129910

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0711

Gnomad ASJ exome AF: 0.00710

Gnomad EAS exome AF: 0.196

Gnomad SAS exome AF: 0.0386

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0752

Gnomad OTH exome AF: 0.0734

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00857 AC: 11245 AN: 1311838 Hom.: 291 Cov.: 31 AF XY: 0.00867 AC XY: 5646 AN XY: 651202

Gnomad4 AFR exome AF: 0.0305

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.0358

Gnomad4 SAS exome AF: 0.0133

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.00644

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.0133 AC: 1188 AN: 89102 Hom.: 32 Cov.: 12 AF XY: 0.0136 AC XY: 585 AN XY: 42880

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.00803

Gnomad4 ASJ AF: 0.00226

Gnomad4 EAS AF: 0.0229

Gnomad4 SAS AF: 0.00450

Gnomad4 FIN AF: 0.00792

Gnomad4 NFE AF: 0.00707

Gnomad4 OTH AF: 0.0130

Alfa AF: 0.0342 Hom.: 53

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	14
Dann	Benign	0.88

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: rs17881210; hg19: chr6-31324448; COSMIC: COSV69523556; COSMIC: COSV69523556;