rs17206855

Positions:

• chr6-31463762-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460889.5(HCP5):​n.406T>C 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 0.0194 in 434,256 control chromosomes in the GnomAD database, including 276 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 0.024 (120 hom., cov: 32)
  • Exomes 𝑓: 0.017 (156 hom.)
• Consequence: HCP5 ENST00000460889.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

HCP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCP5	NR_040662.1	n.492T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCP5	ENST00000541196.3	n.197+254T>C		intron_variant		1
HCP5	ENST00000414046.3	n.502T>C		non_coding_transcript_exon_variant	2/2	4
HCP5	ENST00000460889.5	n.406T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3664 AN: 151876 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00657

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0156 AC: 2614 AN: 167452 Hom.: 86 AF XY: 0.0162 AC XY: 1447 AN XY: 89458

Gnomad AFR exome AF: 0.0601

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.0158

Gnomad EAS exome AF: 0.0103

Gnomad SAS exome AF: 0.0542

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00627

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0169 AC: 4780 AN: 282262 Hom.: 156 Cov.: 0 AF XY: 0.0209 AC XY: 3353 AN XY: 160510

Gnomad4 AFR exome AF: 0.0604

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.0117

Gnomad4 SAS exome AF: 0.0559

Gnomad4 FIN exome AF: 0.00258

Gnomad4 NFE exome AF: 0.00581

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0241 AC: 3665 AN: 151994 Hom.: 120 Cov.: 32 AF XY: 0.0244 AC XY: 1816 AN XY: 74330

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00678

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00643

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0128 Hom.: 54

Bravo AF: 0.0264

Asia WGS AF: 0.0370 AC: 128 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.092

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17206855; hg19: chr6-31431539; COSMIC: COSV69993903;