rs2255221

Positions:

• chr6-31463914-G-T

Variant summary

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

The ENST00000414046.3(HCP5):​n.654G>T 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 0.0729 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 ENST00000414046.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

HCP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCP5	NR_040662.1	n.644G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCP5	ENST00000541196.3	n.198-139G>T		intron_variant		1
HCP5	ENST00000414046.3	n.654G>T		non_coding_transcript_exon_variant	2/2	4
HCP5	ENST00000670109.1	n.617G>T		non_coding_transcript_exon_variant	2/2

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

GnomAD3 exomes AF: 0.0692 AC: 16818 AN: 242966 Hom.: 1071 AF XY: 0.0642 AC XY: 8455 AN XY: 131736

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 SAS exome AF: 0.0128

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

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0713

Gnomad4 OTH exome AF: 0.0717

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0163

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0774

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0829 Hom.: 1124

Bravo AF: 0.113

Asia WGS AF: 0.0290 AC: 102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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