6-32445274-A-G

Variant names:

• chr6-32445274-A-G
• rs3135388
• ENST00000766007.1:n.163-7014T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000766007.1(ENSG00000299747):​n.163-7014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,174 control chromosomes in the GnomAD database, including 62,652 homozygotes. 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 0.91 (62652 hom., cov: 30)
• Consequence: ENSG00000299747 ENST00000766007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 223 publications found

Genes affected

ENSG00000299747 (HGNC:):

HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000766007.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.*634A>G		downstream_gene	N/A	NP_061984.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000299747	ENST00000766007.1		n.163-7014T>C		intron	N/A
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.*634A>G		downstream_gene	N/A	ENSP00000378786.2
	HLA-DRA	ENST00000374982.5	TSL:6	c.*634A>G		downstream_gene	N/A	ENSP00000364121.5

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137778 AN: 152056 Hom.: 62599 Cov.: 30

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.906 AC: 137889 AN: 152174 Hom.: 62652 Cov.: 30 AF XY: 0.908 AC XY: 67510 AN XY: 74376

African (AFR) AF: 0.953 AC: 39583 AN: 41526

American (AMR) AF: 0.928 AC: 14188 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3392 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5169 AN: 5188

South Asian (SAS) AF: 0.980 AC: 4724 AN: 4818

European-Finnish (FIN) AF: 0.872 AC: 9221 AN: 10580

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58532 AN: 67988

Other (OTH) AF: 0.933 AC: 1970 AN: 2112

Alfa AF: 0.884 Hom.: 235119

Bravo AF: 0.913

Asia WGS AF: 0.981 AC: 3413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.55
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3135388; hg19: chr6-32413051;