rs584677

Positions:

• chr6-75586399-G-A

Variant summary

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

The ENST00000402607.2(H3P27):​n.278G>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 0.276 in 258,590 control chromosomes in the GnomAD database, including 11,028 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 0.31 (8237 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2791 hom.)
• Consequence: H3P27 ENST00000402607.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

Genes affected

H3P27 (HGNC:54460): (H3 histone pseudogene 27)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H3P27	ENST00000402607.2	n.278G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47781 AN: 151938 Hom.: 8235 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.220 AC: 23461 AN: 106534 Hom.: 2791 Cov.: 0 AF XY: 0.226 AC XY: 15052 AN XY: 66726

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.314 AC: 47803 AN: 152056 Hom.: 8237 Cov.: 32 AF XY: 0.318 AC XY: 23623 AN XY: 74334

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.281

Alfa AF: 0.285 Hom.: 807

Bravo AF: 0.311

Asia WGS AF: 0.307 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.6
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs584677; hg19: chr6-76296115;