rs198829

Variant names:

• chr6-26118665-A-G
• rs198829
• ENST00000314332.5:c.*10-3530T>C

Variant summary

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

The ENST00000314332.5(H2BC4):​c.*10-3530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,006 control chromosomes in the GnomAD database, including 16,928 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 0.46 (16928 hom., cov: 32)
• Consequence: H2BC4 ENST00000314332.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2BC4	NM_001381989.1	c.*10-3530T>C		intron_variant	Intron 1 of 1		NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000314332.5	c.*10-3530T>C		intron_variant	Intron 1 of 1	1		ENSP00000321744.4
H2BC4	ENST00000707188.1	n.*9+4850T>C		intron_variant	Intron 1 of 2			ENSP00000516775.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69906 AN: 151888 Hom.: 16916 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.460 AC: 69955 AN: 152006 Hom.: 16928 Cov.: 32 AF XY: 0.457 AC XY: 33986 AN XY: 74306

African (AFR) AF: 0.334 AC: 13830 AN: 41450

American (AMR) AF: 0.446 AC: 6820 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1496 AN: 5168

South Asian (SAS) AF: 0.418 AC: 2012 AN: 4818

European-Finnish (FIN) AF: 0.550 AC: 5806 AN: 10556

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.542 AC: 36851 AN: 67958

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.495 Hom.: 27463

Bravo AF: 0.446

Asia WGS AF: 0.408 AC: 1417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs198829; hg19: chr6-26118893;