rs2395029

Variant names:

• chr6-31464003-T-G
• rs2395029
• ENST00000541196.3:n.198-50T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 B:1
• Conservation: PhyloP100: 0.180

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check. 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
HCP5	NR_040662.1	n.733T>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCP5	ENST00000541196.3	n.198-50T>G		intron_variant	Intron 2 of 3	1
HCP5	ENST00000414046.3	n.743T>G		non_coding_transcript_exon_variant	Exon 2 of 2	4
HCP5	ENST00000670109.1	n.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

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

GnomAD2 exomes AF: 0.0270 AC: 6123 AN: 226874 AF XY: 0.0292

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 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

Gnomad4 AFR exome AF: 0.00989 AC: 95 AN: 9604

Gnomad4 AMR exome AF: 0.00951 AC: 295 AN: 31010

Gnomad4 ASJ exome AF: 0.0431 AC: 459 AN: 10656

Gnomad4 EAS exome AF: 0.00245 AC: 30 AN: 12266

Gnomad4 SAS exome AF: 0.0469 AC: 2981 AN: 63524

Gnomad4 FIN exome AF: 0.0107 AC: 342 AN: 32020

Gnomad4 NFE exome AF: 0.0338 AC: 6176 AN: 182768

Gnomad4 Remaining exome AF: 0.0319 AC: 506 AN: 15844

GnomAD4 genome AF: 0.0247 AC: 3749 AN: 152004 Hom.: 63 Cov.: 32 AF XY: 0.0241 AC XY: 1788 AN XY: 74312

Gnomad4 AFR AF: 0.00766 AC: 0.00765774 AN: 0.00765774

Gnomad4 AMR AF: 0.0139 AC: 0.0139126 AN: 0.0139126

Gnomad4 ASJ AF: 0.0428 AC: 0.0427746 AN: 0.0427746

Gnomad4 EAS AF: 0.00853 AC: 0.00852713 AN: 0.00852713

Gnomad4 SAS AF: 0.0484 AC: 0.0484407 AN: 0.0484407

Gnomad4 FIN AF: 0.00932 AC: 0.00932379 AN: 0.00932379

Gnomad4 NFE AF: 0.0367 AC: 0.036689 AN: 0.036689

Gnomad4 OTH AF: 0.0251 AC: 0.0250947 AN: 0.0250947

Alfa AF: 0.0308 Hom.: 289

Bravo AF: 0.0239

Asia WGS AF: 0.0220 AC: 76 AN: 3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism spectrum disorder Pathogenic:1

Jul 28, 2023

Gene Friend Way, National Innovation Center

Significance: Likely risk allele

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 Benign:1

Mar 07, 2025

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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

Other links and lift over

dbSNP: rs2395029; hg19: chr6-31431780;