chr6-32953997-T-G

Variant names:

• chr6-32953997-T-G
• rs3135029
• ENST00000422832.1:c.-11-3194A>C

Variant summary

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

The ENST00000422832.1(HLA-DMA):​c.-11-3194A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,286 control chromosomes in the GnomAD database, including 66,295 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 0.93 (66295 hom., cov: 32)
• Consequence: HLA-DMA ENST00000422832.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 38 publications found

Genes affected

HLA-DMA (HGNC:4934): (major histocompatibility complex, class II, DM alpha) HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422832.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMA	ENST00000422832.1	TSL:6	c.-11-3194A>C		intron	N/A	ENSP00000403122.1
	HLA-DMA	ENST00000464392.1	TSL:6	n.301-4108A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141795 AN: 152168 Hom.: 66237 Cov.: 32

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.937

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.932 AC: 141911 AN: 152286 Hom.: 66295 Cov.: 32 AF XY: 0.931 AC XY: 69350 AN XY: 74454

African (AFR) AF: 0.981 AC: 40755 AN: 41548

American (AMR) AF: 0.897 AC: 13718 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3385 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4245 AN: 5186

South Asian (SAS) AF: 0.979 AC: 4725 AN: 4826

European-Finnish (FIN) AF: 0.921 AC: 9767 AN: 10610

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62169 AN: 68030

Other (OTH) AF: 0.948 AC: 2005 AN: 2116

Alfa AF: 0.922 Hom.: 190942

Bravo AF: 0.929

Asia WGS AF: 0.922 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.47
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs3135029; hg19: chr6-32921774;