6-31463914-G-T

Variant names:

• chr6-31463914-G-T
• rs2255221
• ENST00000541196.3:n.198-139G>T

Variant summary

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

The ENST00000541196.3(HCP5):​n.198-139G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 527,838 control chromosomes in the GnomAD database, including 2,374 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 0.098 (1018 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1356 hom.)
• Consequence: HCP5 ENST00000541196.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 40 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541196.3. 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.644G>T		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.198-139G>T		intron	N/A
	HCP5	ENST00000414046.3	TSL:4	n.654G>T		non_coding_transcript_exon	Exon 2 of 2
	HCP5	ENST00000670109.1		n.617G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 14893 AN: 151700 Hom.: 1018 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.0692 AC: 16818 AN: 242966 AF XY: 0.0642

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0722

Gnomad OTH exome AF: 0.0927

GnomAD4 exome AF: 0.0628 AC: 23603 AN: 376020 Hom.: 1356 Cov.: 0 AF XY: 0.0574 AC XY: 12314 AN XY: 214602

African (AFR) AF: 0.153 AC: 1571 AN: 10246

American (AMR) AF: 0.105 AC: 3603 AN: 34446

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 1938 AN: 11498

East Asian (EAS) AF: 0.0229 AC: 293 AN: 12800

South Asian (SAS) AF: 0.0132 AC: 867 AN: 65900

European-Finnish (FIN) AF: 0.0129 AC: 415 AN: 32264

Middle Eastern (MID) AF: 0.0751 AC: 213 AN: 2838

European-Non Finnish (NFE) AF: 0.0713 AC: 13522 AN: 189560

Other (OTH) AF: 0.0717 AC: 1181 AN: 16468

GnomAD4 genome AF: 0.0981 AC: 14890 AN: 151818 Hom.: 1018 Cov.: 32 AF XY: 0.0930 AC XY: 6900 AN XY: 74208

African (AFR) AF: 0.158 AC: 6530 AN: 41298

American (AMR) AF: 0.127 AC: 1935 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3460

East Asian (EAS) AF: 0.0163 AC: 84 AN: 5146

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4810

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0774 AC: 5264 AN: 67968

Other (OTH) AF: 0.122 AC: 258 AN: 2108

Alfa AF: 0.0845 Hom.: 2672

Bravo AF: 0.113

Asia WGS AF: 0.0290 AC: 102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs2255221; hg19: chr6-31431691; COSMIC: COSV69992164;