Genetic Variant NM_006120.4:c.374-314C>T (chr6-32950203-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006120.4(HLA-DMA):c.374-314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 590,262 control chromosomes in the GnomAD database, including 776 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 0.039 ( 159 hom., cov: 32)

Exomes 𝑓: 0.046 ( 617 hom. )

Consequence

HLA-DMA
NM_006120.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

13 publications found

Variant links:

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]

HLA-DMA links:

ENSG00000248993 (HGNC:):

ENSG00000248993 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DMA	NM_006120.4 link	c.374-314C>T		intron_variant	Intron 2 of 4	ENST00000374843.9	NP_006111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DMA	ENST00000374843.9 link	c.374-314C>T		intron_variant	Intron 2 of 4	6	NM_006120.4	ENSP00000363976.4
ENSG00000248993	ENST00000429234.1 link	c.88+2746C>T		intron_variant	Intron 1 of 3	2		ENSP00000412457.1

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5900

AN:

152190

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0371

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0345

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0588

Gnomad OTH

AF:

0.0378

GnomAD4 exome

AF:

0.0463

AC:

20283

AN:

437954

Hom.:

617

Cov.:

AF XY:

0.0462

AC XY:

10619

AN XY:

229882

show subpopulations

African (AFR)

AF:

0.0121

AC:

149

AN:

12300

American (AMR)

AF:

0.0297

AC:

531

AN:

17854

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

297

AN:

13612

East Asian (EAS)

AF:

0.00164

AC:

AN:

30578

South Asian (SAS)

AF:

0.0362

AC:

1531

AN:

42282

European-Finnish (FIN)

AF:

0.0431

AC:

1245

AN:

28872

Middle Eastern (MID)

AF:

0.0441

AC:

AN:

1950

European-Non Finnish (NFE)

AF:

0.0576

AC:

15255

AN:

264864

Other (OTH)

AF:

0.0444

AC:

1139

AN:

25642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

985

1971

2956

3942

4927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0387

AC:

5899

AN:

152308

Hom.:

159

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41560

American (AMR)

AF:

0.0370

AC:

567

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

AN:

3470

East Asian (EAS)

AF:

0.00405

AC:

AN:

5188

South Asian (SAS)

AF:

0.0348

AC:

168

AN:

4830

European-Finnish (FIN)

AF:

0.0441

AC:

468

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0588

AC:

3999

AN:

68020

Other (OTH)

AF:

0.0369

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

294

588

882

1176

1470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0475

Hom.:

479

Bravo

AF:

0.0360

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0080

(source)

DANN

Benign

0.34

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over