rs17881210

Variant names:

• chr6-31356671-G-A
• rs17881210
• NM_005514.8:c.343+17C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31356671-G-A
• chr6-31356671-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005514.8(HLA-B):​c.343+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• Publications: 10 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.343+17C>T		intron_variant	Intron 2 of 7	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.343+17C>T		intron_variant	Intron 2 of 7	6	NM_005514.8	ENSP00000399168.2

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

GnomAD2 exomes AF: 0.0833 AC: 19872 AN: 238624 AF XY: 0.0785

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0305 AC: 880 AN: 28816

American (AMR) AF: 0.0110 AC: 446 AN: 40438

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 59 AN: 24456

East Asian (EAS) AF: 0.0358 AC: 1114 AN: 31110

South Asian (SAS) AF: 0.0133 AC: 1060 AN: 79890

European-Finnish (FIN) AF: 0.0150 AC: 598 AN: 39854

Middle Eastern (MID) AF: 0.00932 AC: 46 AN: 4936

European-Non Finnish (NFE) AF: 0.00644 AC: 6493 AN: 1008800

Other (OTH) AF: 0.0103 AC: 549 AN: 53538

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0295 AC: 684 AN: 23150

American (AMR) AF: 0.00803 AC: 70 AN: 8716

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 6 AN: 2654

East Asian (EAS) AF: 0.0229 AC: 58 AN: 2538

South Asian (SAS) AF: 0.00450 AC: 10 AN: 2222

European-Finnish (FIN) AF: 0.00792 AC: 47 AN: 5932

Middle Eastern (MID) AF: 0.00575 AC: 1 AN: 174

European-Non Finnish (NFE) AF: 0.00707 AC: 297 AN: 41980

Other (OTH) AF: 0.0130 AC: 15 AN: 1154

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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