chr6-32953997-T-G

Position:

• chr6-32953997-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DMA	ENST00000422832.1	c.-11-3194A>C		intron_variant
HLA-DMA	ENST00000464392.1	n.301-4108A>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.948

Alfa AF: 0.919 Hom.: 113743

Bravo AF: 0.929

Asia WGS AF: 0.922 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3135029; hg19: chr6-32921774;