6-27842848-T-C

Variant summary

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

The ENST00000606613.1(H2BC15):c.475+1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,718 control chromosomes in the GnomAD database, including 1,063 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 0.11 (1063 hom., cov: 30)
• Consequence: H2BC15 ENST00000606613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H2BC15	ENST00000606613.1	c.475+1187T>C		intron_variant		1
H2BC15	ENST00000449538.3	c.*121+1187T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16791 AN: 150610 Hom.: 1062 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.0806

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0896

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16798 AN: 150718 Hom.: 1063 Cov.: 30 AF XY: 0.107 AC XY: 7862 AN XY: 73626

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.0806

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0887

Alfa AF: 0.107 Hom.: 671

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.39
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs175597; hg19: chr6-27810626;