rs198833

Variant names:

• chr6-26114280-G-A
• rs198833
• NM_001381989.1:c.*865C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.9).
• 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 rank	MANE	Protein	UniProt
H2BC4	NM_001381989.1	c.*865C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000707188.1	n.*9+9235C>T		intron_variant	Intron 1 of 2			ENSP00000516775.1

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

African (AFR) AF: 0.880 AC: 36529 AN: 41528

American (AMR) AF: 0.876 AC: 13390 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2996 AN: 3470

East Asian (EAS) AF: 0.972 AC: 5036 AN: 5180

South Asian (SAS) AF: 0.919 AC: 4438 AN: 4828

European-Finnish (FIN) AF: 0.904 AC: 9568 AN: 10588

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57394 AN: 67984

Other (OTH) AF: 0.838 AC: 1764 AN: 2106

Alfa AF: 0.852 Hom.: 14932

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
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs198833; hg19: chr6-26114508;