6-26103170-A-T

Variant names:

• chr6-26103170-A-T
• rs198855
• ENST00000957524.1:c.*10-12136T>A

Variant summary

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

The ENST00000957524.1(H2BC4):​c.*10-12136T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,092 control chromosomes in the GnomAD database, including 41,478 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 0.74 (41478 hom., cov: 31)
• Consequence: H2BC4 ENST00000957524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000957524.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC4	ENST00000957524.1		c.*10-12136T>A		intron	N/A	ENSP00000627583.1
	H2BC4	ENST00000707188.1		n.*10-12136T>A		intron	N/A	ENSP00000516775.1	P62807

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111889 AN: 151974 Hom.: 41435 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.736 AC: 111985 AN: 152092 Hom.: 41478 Cov.: 31 AF XY: 0.740 AC XY: 55048 AN XY: 74372

African (AFR) AF: 0.733 AC: 30398 AN: 41468

American (AMR) AF: 0.743 AC: 11341 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4708 AN: 5176

South Asian (SAS) AF: 0.713 AC: 3440 AN: 4828

European-Finnish (FIN) AF: 0.802 AC: 8486 AN: 10582

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48947 AN: 67978

Other (OTH) AF: 0.704 AC: 1484 AN: 2108

Alfa AF: 0.724 Hom.: 4972

Bravo AF: 0.733

Asia WGS AF: 0.802 AC: 2787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.063
DANN	Benign	0.57
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs198855; hg19: chr6-26103398;