Variant rs2395029 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NR_040662.1(HCP5):n.733T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 512,480 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele,risk factor (no stars).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 32)

Exomes 𝑓: 0.030 ( 305 hom. )

Consequence

HCP5
NR_040662.1 non_coding_transcript_exon

Scores

Clinical Significance

Pathogenic/Likely risk allele; risk factor no assertion criteria provided P:2O:1

Conservation

PhyloP100: 0.180

Variant links:

Genes affected

HCP5 (HGNC:21659): (HLA complex P5)

HCP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0247 (3749/152004) while in subpopulation SAS AF= 0.0484 (233/4810). AF 95% confidence interval is 0.0433. There are 63 homozygotes in gnomad4. There are 1788 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCP5	NR_040662.1 linkuse as main transcript	n.733T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCP5	ENST00000666495.2 linkuse as main transcript	n.95+724T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3750

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00761

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0428

Gnomad EAS

AF:

0.00851

Gnomad SAS

AF:

0.0492

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0254

GnomAD3 exomes

AF:

0.0270

AC:

6123

AN:

226874

Hom.:

161

AF XY:

0.0292

AC XY:

3603

AN XY:

123380

show subpopulations

Gnomad AFR exome

AF:

0.00788

Gnomad AMR exome

AF:

0.00953

Gnomad ASJ exome

AF:

0.0446

Gnomad EAS exome

AF:

0.00314

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.00946

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0284

GnomAD4 exome

AF:

0.0304

AC:

10943

AN:

360476

Hom.:

305

Cov.:

AF XY:

0.0323

AC XY:

6673

AN XY:

206568

show subpopulations

Gnomad4 AFR exome

AF:

0.00989

Gnomad4 AMR exome

AF:

0.00951

Gnomad4 ASJ exome

AF:

0.0431

Gnomad4 EAS exome

AF:

0.00245

Gnomad4 SAS exome

AF:

0.0469

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0247

AC:

3749

AN:

152004

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1788

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00766

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.0428

Gnomad4 EAS

AF:

0.00853

Gnomad4 SAS

AF:

0.0484

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0337

Hom.:

202

Bravo

AF:

0.0239

Asia WGS

AF:

0.0220

AC:

AN:

3476

ClinVar

Significance: Pathogenic/Likely risk allele; risk factor

Submissions summary: Pathogenic:2Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Drug-induced liver injury due to flucloxacillin

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2009

- -

Autism spectrum disorder

Pathogenic:1

Likely risk allele, no assertion criteria provided

clinical testing

Gene Friend Way, National Innovation Center

Jul 28, 2023

A mutation in HLA complex P5. Many recent studies have shown that HCP5 SNP sequences are strongly associated with various chronic and infectious diseases. Several alleles of HLA genes has been reported to be associated with autism, intellectual disability, schizophrenia (PMID: 30976114). rs2395029 is in complete linkage disequilibrium with HLA-B*5701 (PMID: 31421661), which is a risk allele of intellectual disability (PMID: 30976114). -

Abacavir hypersensitivity

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.7

DANN

Benign

0.20

Splicing

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