rs12206204

chr6-26116754-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000314332.5(H2BC4):c.*10-1619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,264 control chromosomes in the GnomAD database, including 23 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 0.012 (23 hom., cov: 32)
• Consequence: H2BC4 ENST00000314332.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

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=-0.85).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0115 (1755/152264) while in subpopulation SAS AF= 0.0243 (117/4812). AF 95% confidence interval is 0.0207. There are 23 homozygotes in gnomad4. There are 829 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H2BC4	NM_001381989.1	c.*10-1619G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H2BC4	ENST00000314332.5	c.*10-1619G>A		intron_variant		1		P1
H2BC4	ENST00000707188.1	c.*9+6761G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1756 AN: 152146 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.00861

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

GnomAD4 genome AF: 0.0115 AC: 1755 AN: 152264 Hom.: 23 Cov.: 32 AF XY: 0.0111 AC XY: 829 AN XY: 74440

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.00744

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.0154 Hom.: 40

Bravo AF: 0.0106

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.5
Dann	Benign	0.67

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: rs12206204; hg19: chr6-26116982;