Variant 6-33008236-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002119.4(HLA-DOA):c.108C>T(p.Pro36Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,612,572 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 39 hom. )

Consequence

HLA-DOA
NM_002119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

HLA-DOA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 6-33008236-G-A is Benign according to our data. Variant chr6-33008236-G-A is described in ClinVar as [Benign]. Clinvar id is 768080.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1872/152298) while in subpopulation AFR AF= 0.0423 (1758/41570). AF 95% confidence interval is 0.0406. There are 30 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4 linkuse as main transcript	c.108C>T	p.Pro36Pro	synonymous_variant	2/5	ENST00000229829.7	NP_002110.1	P06340X5CF87A0A1V0E3Q8A0A1V0E3Q5A0A1V0E3N1A0A1V0E3M7A0A1V0E3R3A0A1V0E3S6A0A1V0E3T1A0A1V0E3P8A0A1V0E3Q2A0A1V0E3P6A0A1V0E3S7A0A1V0E3P1A0A1V0E3Q6A0A1V0E3P3A0A1V0E3R6A0A1V0E3P9A0A1V0E3N7A0A1V0E3S0A0A1V0E3Q1A0A1V0E3N3A0A1V0E3Q4A0A1V0E3R4A0A1V0E3P0A0A1V0E3R0A0A1V0E3N6A0A1V0E3R8A0A1V0E3S4A0A1V0E3Q7A0A1V0E3Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HLA-DOA	ENST00000229829.7 linkuse as main transcript	c.108C>T	p.Pro36Pro	synonymous_variant	2/5	6	NM_002119.4	ENSP00000229829.3	P06340
HLA-DOA	ENST00000374813.1 linkuse as main transcript	c.83-142C>T		intron_variant		6		ENSP00000363946.1	F6WU08
HLA-DOA	ENST00000467465.1 linkuse as main transcript	n.297C>T		non_coding_transcript_exon_variant	2/2	6

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1870

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00326

AC:

800

AN:

245624

Hom.:

AF XY:

0.00223

AC XY:

299

AN XY:

133964

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00253

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000500

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.00160

AC:

2338

AN:

1460274

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1004

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000766

Gnomad4 NFE exome

AF:

0.000431

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.0123

AC:

1872

AN:

152298

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

857

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0141

EpiCase

AF:

0.000818

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.4

DANN

Benign

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over