chr6-31355522-C-A

Variant names:

• chr6-31355522-C-A
• rs7769258
• NM_005514.8:c.690G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_005514.8(HLA-B):​c.690G>T​(p.Leu230Leu) 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.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 10)
  • 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: -0.166
• 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]

ENSG00000298396 (HGNC:):

MIR6891 (HGNC:50243): (microRNA 6891) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.166 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.690G>T	p.Leu230Leu	synonymous	Exon 4 of 8	NP_005505.2
	MIR6891	NR_106951.1		n.-206G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.690G>T	p.Leu230Leu	synonymous	Exon 4 of 8	ENSP00000399168.2	P01889
	HLA-B	ENST00000696559.1		c.690G>T	p.Leu230Leu	synonymous	Exon 7 of 11	ENSP00000512717.1	P01889
	HLA-B	ENST00000696560.1		c.690G>T	p.Leu230Leu	synonymous	Exon 6 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 83172 Hom.: 0 Cov.: 10

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

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1369496 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 684996

African (AFR) AF: 0.00 AC: 0 AN: 30656

American (AMR) AF: 0.00 AC: 0 AN: 43284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24782

East Asian (EAS) AF: 0.00 AC: 0 AN: 37942

South Asian (SAS) AF: 0.00 AC: 0 AN: 84496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035688

Other (OTH) AF: 0.00 AC: 0 AN: 56308

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 83172 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 39586

African (AFR) AF: 0.00 AC: 0 AN: 18230

American (AMR) AF: 0.00 AC: 0 AN: 6688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2006

East Asian (EAS) AF: 0.00 AC: 0 AN: 2632

South Asian (SAS) AF: 0.00 AC: 0 AN: 1782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44396

Other (OTH) AF: 0.00 AC: 0 AN: 882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.17
PromoterAI		0.026	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7769258; hg19: chr6-31323299;