rs933199

chr6-26112665-T-C

Variant summary

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

The ENST00000707188.1(H2BC4):c.*9+10850A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,206 control chromosomes in the GnomAD database, including 1,789 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 (1789 hom., cov: 32)
• Consequence: H2BC4 ENST00000707188.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

Genes affected

H2BC4 (HGNC:4757): (H2B clustered histone 4) 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. The protein has antibacterial and antifungal antimicrobial activity. The main transcript variant of this gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. This transcript variant lacks a polyA tail but instead contains a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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
H2BC4	ENST00000707188.1	c.*9+10850A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17465 AN: 152088 Hom.: 1783 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.115 AC: 17488 AN: 152206 Hom.: 1789 Cov.: 32 AF XY: 0.127 AC XY: 9457 AN XY: 74424

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.0629

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0785 Hom.: 871

Bravo AF: 0.114

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.2
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs933199; hg19: chr6-26112893;