6-26103170-A-T

Position:

• chr6-26103170-A-T

Variant summary

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

The ENST00000707188.1(H2BC4):​c.*10-12136T>A variant causes a intron, NMD transcript 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 ENST00000707188.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000707188.1	c.*10-12136T>A		intron_variant, NMD_transcript_variant				ENSP00000516775

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

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.704

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs198855; hg19: chr6-26103398;