rs3918148

Variant names:

• chr6-32968485-C-G
• rs3918148
• ENST00000422832.1:c.-12+517G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32968485-C-G
• chr6-32968485-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000422832.1(HLA-DMA):​c.-12+517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,458 control chromosomes in the GnomAD database, including 62 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 0.024 (62 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: HLA-DMA ENST00000422832.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 0 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]

LOC124901302 (HGNC:):

BRD2 (HGNC:1103): (bromodomain containing 2) This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0237 (3605/152364) while in subpopulation SAS AF = 0.0389 (188/4832). AF 95% confidence interval is 0.0344. There are 62 homozygotes in GnomAd4. There are 1726 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 62 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC124901302	NR_190903.1		n.37G>C		non_coding_transcript_exon	Exon 1 of 2
	LOC124901302	NR_190904.1		n.37G>C		non_coding_transcript_exon	Exon 1 of 3
	BRD2	NM_005104.4	MANE Select	c.-1876C>G		upstream_gene	N/A	NP_005095.1	P25440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMA	ENST00000422832.1	TSL:6	c.-12+517G>C		intron	N/A	ENSP00000403122.1	F6S093
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.-1876C>G		upstream_gene	N/A	ENSP00000363958.4	P25440-1
	HLA-DMA	ENST00000464392.1	TSL:6	n.-41G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3605 AN: 152246 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0106 AC: 1 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.0143 AC XY: 1 AN XY: 70

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0125 AC: 1 AN: 80

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0237 AC: 3605 AN: 152364 Hom.: 62 Cov.: 33 AF XY: 0.0232 AC XY: 1726 AN XY: 74508

African (AFR) AF: 0.00647 AC: 269 AN: 41598

American (AMR) AF: 0.0244 AC: 374 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5178

South Asian (SAS) AF: 0.0389 AC: 188 AN: 4832

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2391 AN: 68032

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0233

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.51
PromoterAI		-0.082	Neutral

Splicing

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: rs3918148;

hg19: chr6-32936262;