rs198829

Positions:

• chr6-26118665-A-G

Variant summary

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

The NM_001381989.1(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 NM_001381989.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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 (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2BC4	NM_001381989.1	c.*10-3530T>C		intron_variant			NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000314332.5	c.*10-3530T>C		intron_variant		1		ENSP00000321744.4
H2BC4	ENST00000707188.1	n.*9+4850T>C		intron_variant				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

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.413

Alfa AF: 0.511 Hom.: 18705

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs198829; hg19: chr6-26118893;