rs3130907

Positions:

• chr6-31464036-A-G
• chr6-31464036-A-T

Variant summary

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

The ENST00000541196.3(HCP5):​n.198-17A>G variant causes a splice polypyrimidine tract, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 446,478 control chromosomes in the GnomAD database, including 2,199 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 0.076 (611 hom., cov: 32)
  • Exomes 𝑓: 0.087 (1588 hom.)
• Consequence: HCP5 ENST00000541196.3 splice_polypyrimidine_tract, intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCP5	NR_040662.1	n.766A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCP5	ENST00000666495.2	n.95+757A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11539 AN: 151714 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0440

Gnomad EAS AF: 0.00523

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0570

GnomAD3 exomes AF: 0.0778 AC: 14363 AN: 184570 Hom.: 806 AF XY: 0.0805 AC XY: 8058 AN XY: 100066

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.0301

Gnomad ASJ exome AF: 0.0424

Gnomad EAS exome AF: 0.00218

Gnomad SAS exome AF: 0.0818

Gnomad FIN exome AF: 0.0772

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0712

GnomAD4 exome AF: 0.0872 AC: 25682 AN: 294646 Hom.: 1588 Cov.: 0 AF XY: 0.0883 AC XY: 14843 AN XY: 168072

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0436

Gnomad4 EAS exome AF: 0.00170

Gnomad4 SAS exome AF: 0.0858

Gnomad4 FIN exome AF: 0.0818

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0812

GnomAD4 genome AF: 0.0760 AC: 11543 AN: 151832 Hom.: 611 Cov.: 32 AF XY: 0.0720 AC XY: 5340 AN XY: 74216

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0440

Gnomad4 EAS AF: 0.00505

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0574

Alfa AF: 0.103 Hom.: 937

Bravo AF: 0.0700

Asia WGS AF: 0.0230 AC: 82 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3130907; hg19: chr6-31431813;