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 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
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCP5	NR_040662.1		n.733T>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCP5	ENST00000541196.3	TSL:1	n.198-50T>G		intron	N/A
	HCP5	ENST00000414046.3	TSL:4	n.743T>G		non_coding_transcript_exon	Exon 2 of 2
	HCP5	ENST00000670109.1		n.706T>G		non_coding_transcript_exon	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

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Abacavir hypersensitivity (1)
-	-	-	Autism spectrum disorder (1)

Computational scores

Source: dbNSFP v4.9

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;