6-31357118-G-T

Variant names:

• chr6-31357118-G-T
• rs1131156
• NM_005514.8:c.41C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005514.8(HLA-B):​c.41C>A​(p.Ser14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 27 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	NM_005514.8	MANE Select	c.41C>A	p.Ser14*	stop_gained	Exon 1 of 8	NP_005505.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.41C>A	p.Ser14*	stop_gained	Exon 1 of 8	ENSP00000399168.2	P01889
	HLA-B	ENST00000696559.1		c.41C>A	p.Ser14*	stop_gained	Exon 4 of 11	ENSP00000512717.1	P01889
	HLA-B	ENST00000696560.1		c.41C>A	p.Ser14*	stop_gained	Exon 3 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 802744 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 396054

African (AFR) AF: 0.00 AC: 0 AN: 15238

American (AMR) AF: 0.00 AC: 0 AN: 23968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16474

East Asian (EAS) AF: 0.00 AC: 0 AN: 14466

South Asian (SAS) AF: 0.00 AC: 0 AN: 33948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 638026

Other (OTH) AF: 0.00 AC: 0 AN: 33066

GnomAD4 genome Cov.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	38
DANN	Benign	0.94
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.011	N
PhyloP100		-0.073
Vest4		0.41
GERP RS		1.5
PromoterAI		-0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=163/37	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1131156; hg19: chr6-31324895;