rs198833

chr6-26114280-G-A

Variant summary

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

The NM_001381989.1(H2BC4):c.*865C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,172 control chromosomes in the GnomAD database, including 57,534 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 0.87 (57534 hom., cov: 31)
• Consequence: H2BC4 NM_001381989.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H2BC4	NM_001381989.1	c.*865C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H2BC4	ENST00000707188.1	c.*9+9235C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132101 AN: 152054 Hom.: 57486 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.869 AC: 132204 AN: 152172 Hom.: 57534 Cov.: 31 AF XY: 0.873 AC XY: 64929 AN XY: 74382

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.838

Alfa AF: 0.855 Hom.: 7048

Bravo AF: 0.866

Asia WGS AF: 0.925 AC: 3216 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.30
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs198833; hg19: chr6-26114508;