rs13212651

Positions:

• chr6-27839207-A-G

Variant summary

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

The ENST00000606613.1(H2BC15):​c.377+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 1,390,674 control chromosomes in the GnomAD database, including 6,749 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 0.053 (339 hom., cov: 33)
  • Exomes 𝑓: 0.092 (6410 hom.)
• Consequence: H2BC15 ENST00000606613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

Genes affected

H2BC15 (HGNC:4749): (H2B clustered histone 15) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.27839207A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC15	ENST00000606613.1	c.377+169A>G		intron_variant		1		ENSP00000475942.1
H2BC15	ENST00000449538.3	n.*23+142A>G		intron_variant		1		ENSP00000446031.1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8042 AN: 152230 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0920 AC: 113956 AN: 1238326 Hom.: 6410 Cov.: 22 AF XY: 0.0891 AC XY: 53506 AN XY: 600660

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0260

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.0000877

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0418

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0736

GnomAD4 genome AF: 0.0528 AC: 8038 AN: 152348 Hom.: 339 Cov.: 33 AF XY: 0.0476 AC XY: 3544 AN XY: 74508

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0756 Hom.: 487

Bravo AF: 0.0516

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13212651; hg19: chr6-27806985;