6-29945191-C-A

Variant names:

• chr6-29945191-C-A
• rs3823339
• NM_002116.8:c.1046-43C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002116.8(HLA-A):​c.1046-43C>A variant causes a intron 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: 0.0000067 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-A NM_002116.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 11 publications found

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A 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 so that they can be recognized by cytotoxic T cells. 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, exons 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. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002116.8. 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-A	NM_002116.8	MANE Select	c.1046-43C>A		intron	N/A	NP_002107.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	ENST00000376809.10	TSL:6 MANE Select	c.1046-43C>A		intron	N/A	ENSP00000366005.5	P04439-1
	HLA-A	ENST00000952344.1		c.1157-43C>A		intron	N/A	ENSP00000622403.1
	HLA-A	ENST00000706894.1		c.1046-43C>A		intron	N/A	ENSP00000516610.1	A0A9L9PYF9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 76722 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

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248502 AF XY: 0.00

Gnomad AFR exome AF: 0.0000622

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000672 AC: 6 AN: 893230 Hom.: 0 Cov.: 13 AF XY: 0.0000132 AC XY: 6 AN XY: 455068

African (AFR) AF: 0.00 AC: 0 AN: 23068

American (AMR) AF: 0.00 AC: 0 AN: 34206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16350

East Asian (EAS) AF: 0.00 AC: 0 AN: 25324

South Asian (SAS) AF: 0.00 AC: 0 AN: 64294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3488

European-Non Finnish (NFE) AF: 0.00000922 AC: 6 AN: 651100

Other (OTH) AF: 0.00 AC: 0 AN: 38892

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 76722 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 36992

African (AFR) AF: 0.00 AC: 0 AN: 21270

American (AMR) AF: 0.00 AC: 0 AN: 6166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1606

East Asian (EAS) AF: 0.00 AC: 0 AN: 2590

South Asian (SAS) AF: 0.00 AC: 0 AN: 2154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 35566

Other (OTH) AF: 0.00 AC: 0 AN: 1012

Alfa AF: 0.00 Hom.: 214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.51
PhyloP100		-1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3823339; hg19: chr6-29912968;