rs933199

Variant names:

• chr6-26112665-T-C
• rs933199
• ENST00000904681.1:c.*10-474A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000904681.1(H2BC4):​c.*10-474A>G variant causes a intron 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 ENST00000904681.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000904681.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC4	ENST00000904681.1		c.*10-474A>G		intron	N/A	ENSP00000574740.1
	H2BC4	ENST00000957524.1		c.*9+10850A>G		intron	N/A	ENSP00000627583.1
	H2BC4	ENST00000707188.1		n.*9+10850A>G		intron	N/A	ENSP00000516775.1	P62807

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

African (AFR) AF: 0.0956 AC: 3971 AN: 41538

American (AMR) AF: 0.174 AC: 2665 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2881 AN: 5162

South Asian (SAS) AF: 0.197 AC: 951 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2145 AN: 10598

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0629 AC: 4279 AN: 68002

Other (OTH) AF: 0.132 AC: 278 AN: 2112

Alfa AF: 0.0847 Hom.: 1598

Bravo AF: 0.114

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.50
PhyloP100		-0.96

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs933199;

hg19: chr6-26112893;