6-27842848-T-C

Variant names:

• chr6-27842848-T-C
• rs175597
• ENST00000606613.1:c.475+1187T>C

Variant summary

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

The ENST00000606613.1(H2BC15):​c.475+1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,718 control chromosomes in the GnomAD database, including 1,063 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 0.11 (1063 hom., cov: 30)
• Consequence: H2BC15 ENST00000606613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 28 publications found

Genes affected

H2BC15 (HGNC:4749): (H2B clustered histone 15) 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. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606613.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC15	ENST00000606613.1	TSL:1	c.475+1187T>C		intron	N/A	ENSP00000475942.1
	H2BC15	ENST00000449538.3	TSL:1	n.*121+1187T>C		intron	N/A	ENSP00000446031.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16791 AN: 150610 Hom.: 1062 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.0806

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.111 AC: 16798 AN: 150718 Hom.: 1063 Cov.: 30 AF XY: 0.107 AC XY: 7862 AN XY: 73626

African (AFR) AF: 0.153 AC: 6275 AN: 40892

American (AMR) AF: 0.116 AC: 1760 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3466

East Asian (EAS) AF: 0.0806 AC: 416 AN: 5162

South Asian (SAS) AF: 0.0756 AC: 363 AN: 4802

European-Finnish (FIN) AF: 0.0442 AC: 459 AN: 10378

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7089 AN: 67566

Other (OTH) AF: 0.0887 AC: 186 AN: 2098

Alfa AF: 0.119 Hom.: 1637

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs175597; hg19: chr6-27810626;