6-26107235-A-G

Variant names:

• chr6-26107235-A-G
• rs198846
• ENST00000707188.1:n.*10-16201T>C

Variant summary

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

The ENST00000707188.1(H2BC4):​n.*10-16201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,176 control chromosomes in the GnomAD database, including 57,503 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 (57503 hom., cov: 31)
• Consequence: H2BC4 ENST00000707188.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 63 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]

H1-6 (HGNC:4720): (H1.6 linker histone, cluster member) Histones are basic nuclear proteins responsible for 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. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H1-6	NM_005323.4	c.*235T>C		downstream_gene_variant		ENST00000338379.6	NP_005314.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000707188.1	n.*10-16201T>C		intron_variant	Intron 1 of 2			ENSP00000516775.1
H1-6	ENST00000338379.6	c.*235T>C		downstream_gene_variant		6	NM_005323.4	ENSP00000341214.5

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132087 AN: 152058 Hom.: 57456 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.920

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: 132189 AN: 152176 Hom.: 57503 Cov.: 31 AF XY: 0.873 AC XY: 64907 AN XY: 74378

African (AFR) AF: 0.880 AC: 36521 AN: 41522

American (AMR) AF: 0.876 AC: 13392 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3009 AN: 3470

East Asian (EAS) AF: 0.963 AC: 4978 AN: 5168

South Asian (SAS) AF: 0.920 AC: 4431 AN: 4814

European-Finnish (FIN) AF: 0.904 AC: 9583 AN: 10598

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

European-Non Finnish (NFE) AF: 0.844 AC: 57419 AN: 67994

Other (OTH) AF: 0.837 AC: 1767 AN: 2110

Alfa AF: 0.855 Hom.: 233424

Bravo AF: 0.866

Asia WGS AF: 0.923 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.12
DANN	Benign	0.033
PhyloP100		-2.2
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs198846; hg19: chr6-26107463;