6-31464003-T-G

Variant summary

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

The ENST00000414046.3(HCP5):​n.743T>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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 32)
Exomes 𝑓: 0.030 ( 305 hom. )

Consequence

HCP5
ENST00000414046.3 non_coding_transcript_exon

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1B:1

Conservation

PhyloP100: 0.180
Variant links:
Genes affected
HCP5 (HGNC:21659): (HLA complex P5)

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 rank MANE Protein UniProt
HCP5NR_040662.1 linkn.733T>G non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HCP5ENST00000541196.3 linkn.198-50T>G intron_variant Intron 2 of 3 1
HCP5ENST00000414046.3 linkn.743T>G non_coding_transcript_exon_variant Exon 2 of 2 4
HCP5ENST00000670109.1 linkn.706T>G non_coding_transcript_exon_variant Exon 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0247
AC:
3750
AN:
151886
Hom.:
64
Cov.:
32
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.:
0
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.:
63
Cov.:
32
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:
76
AN:
3476

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autism spectrum disorder Pathogenic:1
Likely risk allele, no assertion criteria providedclinical testingGene Friend Way, National Innovation CenterJul 28, 2023A 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 Benign:1
Benign, no assertion criteria providedliterature onlyOMIMMar 07, 2025- -

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.

Other links and lift over

dbSNP: rs2395029; hg19: chr6-31431780; API