chr6-31356716-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005514.8(HLA-B):​c.315G>C​(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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L105L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 6)
  • Exomes 𝑓: 0.0000078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-31356716-C-G is Benign according to our data. Variant chr6-31356716-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.588 with no splicing effect.

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 54834 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000512 AC: 1 AN: 195316 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000783 AC: 8 AN: 1021254 Hom.: 0 Cov.: 29 AF XY: 0.00000398 AC XY: 2 AN XY: 502370

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

African (AFR) AF: 0.00 AC: 0 AN: 18436

American (AMR) AF: 0.00 AC: 0 AN: 31652

Ashkenazi Jewish (ASJ) AF: 0.0000789 AC: 1 AN: 12674

East Asian (EAS) AF: 0.00 AC: 0 AN: 22596

South Asian (SAS) AF: 0.00 AC: 0 AN: 48488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2584

European-Non Finnish (NFE) AF: 0.00000740 AC: 6 AN: 810352

Other (OTH) AF: 0.0000252 AC: 1 AN: 39698

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 54888 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 26342

African (AFR) AF: 0.00 AC: 0 AN: 12520

American (AMR) AF: 0.00 AC: 0 AN: 5036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 978

East Asian (EAS) AF: 0.00 AC: 0 AN: 1636

South Asian (SAS) AF: 0.00 AC: 0 AN: 922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 64

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28346

Other (OTH) AF: 0.00 AC: 0 AN: 702

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.6
DANN	Benign	0.54
PhyloP100		-0.59
PromoterAI		0.025	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;