rs2395029

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The ENST00000541196.3(HCP5):​n.198-50T>G variant causes a intron 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 ENST00000541196.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 B:1
• Conservation: PhyloP100: 0.180
• Publications: 210 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-31464003-T-G is Benign according to our data. Variant chr6-31464003-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 14910.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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 passed quality control check.
• 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

African (AFR) AF: 0.00989 AC: 95 AN: 9604

American (AMR) AF: 0.00951 AC: 295 AN: 31010

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 459 AN: 10656

East Asian (EAS) AF: 0.00245 AC: 30 AN: 12266

South Asian (SAS) AF: 0.0469 AC: 2981 AN: 63524

European-Finnish (FIN) AF: 0.0107 AC: 342 AN: 32020

Middle Eastern (MID) AF: 0.0212 AC: 59 AN: 2784

European-Non Finnish (NFE) AF: 0.0338 AC: 6176 AN: 182768

Other (OTH) 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

African (AFR) AF: 0.00766 AC: 317 AN: 41396

American (AMR) AF: 0.0139 AC: 212 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 148 AN: 3460

East Asian (EAS) AF: 0.00853 AC: 44 AN: 5160

South Asian (SAS) AF: 0.0484 AC: 233 AN: 4810

European-Finnish (FIN) AF: 0.00932 AC: 99 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2495 AN: 68004

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

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
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2395029; hg19: chr6-31431780;