rs13194781

Variant names:

• chr6-27847861-A-G
• rs13194781
• ENST00000606613.1:c.476-4248A>G

Variant summary

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

The ENST00000606613.1(H2BC15):​c.476-4248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,156 control chromosomes in the GnomAD database, including 332 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 0.052 (332 hom., cov: 31)
• Consequence: H2BC15 ENST00000606613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 36 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC15	ENST00000606613.1	c.476-4248A>G		intron_variant	Intron 2 of 2	1		ENSP00000475942.1
H2BC15	ENST00000449538.3	n.*122-4248A>G		intron_variant	Intron 2 of 2	1		ENSP00000446031.1

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7870 AN: 152038 Hom.: 332 Cov.: 31

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0517 AC: 7866 AN: 152156 Hom.: 332 Cov.: 31 AF XY: 0.0467 AC XY: 3471 AN XY: 74402

African (AFR) AF: 0.0139 AC: 576 AN: 41522

American (AMR) AF: 0.0347 AC: 531 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0397 AC: 420 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6054 AN: 67978

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0739 Hom.: 1436

Bravo AF: 0.0502

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-0.41
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: rs13194781; hg19: chr6-27815639;