chr6-27839207-A-G

Variant names:

• chr6-27839207-A-G
• rs13212651
• ENST00000606613.1:c.377+169A>G

Variant summary

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

The ENST00000606613.1(H2BC15):​c.377+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 1,390,674 control chromosomes in the GnomAD database, including 6,749 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 0.053 (339 hom., cov: 33)
  • Exomes 𝑓: 0.092 (6410 hom.)
• Consequence: H2BC15 ENST00000606613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 23 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC15	NM_003520.4	MANE Select	c.*165A>G		downstream_gene	N/A	NP_003511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC15	ENST00000606613.1	TSL:1	c.377+169A>G		intron	N/A	ENSP00000475942.1
	H2BC15	ENST00000449538.3	TSL:1	n.*23+142A>G		intron	N/A	ENSP00000446031.1
	H2BC15	ENST00000898165.1		c.*23+142A>G		intron	N/A	ENSP00000568224.1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8042 AN: 152230 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0920 AC: 113956 AN: 1238326 Hom.: 6410 Cov.: 22 AF XY: 0.0891 AC XY: 53506 AN XY: 600660

African (AFR) AF: 0.0147 AC: 401 AN: 27290

American (AMR) AF: 0.0260 AC: 498 AN: 19164

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 397 AN: 18516

East Asian (EAS) AF: 0.0000877 AC: 3 AN: 34204

South Asian (SAS) AF: 0.000151 AC: 9 AN: 59512

European-Finnish (FIN) AF: 0.0418 AC: 1392 AN: 33322

Middle Eastern (MID) AF: 0.00566 AC: 20 AN: 3534

European-Non Finnish (NFE) AF: 0.108 AC: 107432 AN: 991104

Other (OTH) AF: 0.0736 AC: 3804 AN: 51680

GnomAD4 genome AF: 0.0528 AC: 8038 AN: 152348 Hom.: 339 Cov.: 33 AF XY: 0.0476 AC XY: 3544 AN XY: 74508

African (AFR) AF: 0.0175 AC: 726 AN: 41586

American (AMR) AF: 0.0351 AC: 538 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0399 AC: 424 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0891 AC: 6062 AN: 68022

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0740 Hom.: 925

Bravo AF: 0.0516

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13212651; hg19: chr6-27806985;