Variant 6-32518080-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_002125.4(HLA-DRB5):c.764-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 1)

Exomes 𝑓: 0.000022 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DRB5
NM_002125.4 splice_region, intron

Scores

Splicing: ADA: 0.0001011

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.410

Variant links:

Genes affected

HLA-DRB5 (HGNC:4953): (major histocompatibility complex, class II, DR beta 5) HLA-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene. [provided by RefSeq, Feb 2020]

HLA-DRB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-32518080-G-A is Benign according to our data. Variant chr6-32518080-G-A is described in ClinVar as [Benign]. Clinvar id is 252599.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRB5	NM_002125.4 linkuse as main transcript	c.764-3C>T		splice_region_variant, intron_variant		ENST00000374975.4	NP_002116.2	Q30154A0A2Z4LKS3
HLA-DRB5	XM_011514562.3 linkuse as main transcript	c.764-3C>T		splice_region_variant, intron_variant			XP_011512864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRB5	ENST00000374975.4 linkuse as main transcript	c.764-3C>T		splice_region_variant, intron_variant		6	NM_002125.4	ENSP00000364114.3		Q30154

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

38508

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000346

Gnomad ASJ

AF:

0.00191

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000418

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00235

GnomAD3 exomes

AF:

0.00112

AC:

AN:

71116

Hom.:

AF XY:

0.00130

AC XY:

AN XY:

39218

show subpopulations

Gnomad AFR exome

AF:

0.000223

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00118

Gnomad EAS exome

AF:

0.000192

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00117

Gnomad NFE exome

AF:

0.00194

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000220

AC:

AN:

409344

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

207632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00000325

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000234

AC:

AN:

38524

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

18796

show subpopulations

Gnomad4 AFR

AF:

0.000190

Gnomad4 AMR

AF:

0.000345

Gnomad4 ASJ

AF:

0.00191

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000418

Gnomad4 NFE

AF:

0.000163

Gnomad4 OTH

AF:

0.00226

Alfa

AF:

0.0581

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Oct 13, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.010

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