NM_005514.8:c.315G>A

Variant names:

• chr6-31356716-C-T
• rs41549513
• NM_005514.8:c.315G>A

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.315G>A​(p.Leu105Leu) 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. Synonymous variant affecting the same amino acid position (i.e. L105L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 3 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=-0.91).

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.315G>A	p.Leu105Leu	synonymous	Exon 2 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.315G>A	p.Leu105Leu	synonymous	Exon 2 of 8	ENSP00000399168.2	P01889
	HLA-B	ENST00000696559.1		c.315G>A	p.Leu105Leu	synonymous	Exon 5 of 11	ENSP00000512717.1	P01889
	HLA-B	ENST00000696560.1		c.315G>A	p.Leu105Leu	synonymous	Exon 4 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1021412 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 502436

African (AFR) AF: 0.00 AC: 0 AN: 18438

American (AMR) AF: 0.00 AC: 0 AN: 31658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12674

East Asian (EAS) AF: 0.00 AC: 0 AN: 22600

South Asian (SAS) AF: 0.00 AC: 0 AN: 48490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 810496

Other (OTH) AF: 0.00 AC: 0 AN: 39700

GnomAD4 genome Cov.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.0
DANN	Benign	0.78
PhyloP100		-0.59
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs41549513; hg19: chr6-31324493;