rs2255223

Variant names:

• chr6-31463946-G-A
• rs2255223
• ENST00000541196.3:n.198-107G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414046.3(HCP5):​n.686G>A 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 0.0335 in 530,644 control chromosomes in the GnomAD database, including 566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (197 hom., cov: 32)
  • Exomes 𝑓: 0.031 (369 hom.)
• Consequence: HCP5 ENST00000414046.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 10 publications found

Genes affected

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

ENSG00000288587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

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.676G>A		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.198-107G>A		intron	N/A
	HCP5	ENST00000414046.3	TSL:4	n.686G>A		non_coding_transcript_exon	Exon 2 of 2
	HCP5	ENST00000670109.1		n.649G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6084 AN: 151796 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00437

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0311 AC: 7631 AN: 245252 AF XY: 0.0302

Gnomad AFR exome AF: 0.0374

Gnomad AMR exome AF: 0.0436

Gnomad ASJ exome AF: 0.0274

Gnomad EAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00611

Gnomad NFE exome AF: 0.0436

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0309 AC: 11708 AN: 378730 Hom.: 369 Cov.: 0 AF XY: 0.0287 AC XY: 6189 AN XY: 215946

African (AFR) AF: 0.0366 AC: 379 AN: 10344

American (AMR) AF: 0.0437 AC: 1531 AN: 35072

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 332 AN: 11622

East Asian (EAS) AF: 0.00116 AC: 15 AN: 12952

South Asian (SAS) AF: 0.00426 AC: 282 AN: 66238

European-Finnish (FIN) AF: 0.00684 AC: 221 AN: 32298

Middle Eastern (MID) AF: 0.0120 AC: 34 AN: 2844

European-Non Finnish (NFE) AF: 0.0442 AC: 8433 AN: 190774

Other (OTH) AF: 0.0290 AC: 481 AN: 16586

GnomAD4 genome AF: 0.0400 AC: 6084 AN: 151914 Hom.: 197 Cov.: 32 AF XY: 0.0377 AC XY: 2802 AN XY: 74270

African (AFR) AF: 0.0377 AC: 1559 AN: 41358

American (AMR) AF: 0.0630 AC: 960 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3464

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5152

South Asian (SAS) AF: 0.00437 AC: 21 AN: 4804

European-Finnish (FIN) AF: 0.00538 AC: 57 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3234 AN: 67984

Other (OTH) AF: 0.0479 AC: 101 AN: 2108

Alfa AF: 0.0420 Hom.: 218

Bravo AF: 0.0457

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.8
DANN	Benign	0.59
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs2255223; hg19: chr6-31431723; COSMIC: COSV69992793;