Genetic Variant H2BC15:c.377+169A>G (chr6-27839207-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

Publications

23 publications found

Variant links:

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]

H2BC15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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
H2BC15	NM_003520.4 link	c.*165A>G		downstream_gene_variant		ENST00000612898.2	NP_003511.1	Q99877A0A024RCJ9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
H2BC15	ENST00000606613.1 link	c.377+169A>G	intron_variant	Intron 1 of 2	1		ENSP00000475942.1	U3KQK0
H2BC15	ENST00000449538.3 link	n.*23+142A>G	intron_variant	Intron 1 of 2	1		ENSP00000446031.1	Q99877
H2BC15	ENST00000612898.2 link	c.*165A>G	downstream_gene_variant		6	NM_003520.4	ENSP00000483903.1	Q99877

Frequencies

GnomAD3 genomes

AF:

0.0528

AC:

8042

AN:

152230

Hom.:

339

Cov.:

show subpopulations

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.:

AF XY:

0.0891

AC XY:

53506

AN XY:

600660

show subpopulations

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:

AN:

34204

South Asian (SAS)

AF:

0.000151

AC:

AN:

59512

European-Finnish (FIN)

AF:

0.0418

AC:

1392

AN:

33322

Middle Eastern (MID)

AF:

0.00566

AC:

AN:

3534

European-Non Finnish (NFE)

AF:

0.108

AC:

107432

AN:

991104

Other (OTH)

AF:

0.0736

AC:

3804

AN:

51680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4971

9942

14913

19884

24855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4182

8364

12546

16728

20910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0528

AC:

8038

AN:

152348

Hom.:

339

Cov.:

AF XY:

0.0476

AC XY:

3544

AN XY:

74508

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0399

AC:

424

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0891

AC:

6062

AN:

68022

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

401

801

1202

1602

2003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0740

Hom.:

925

Bravo

AF:

0.0516

Asia WGS

AF:

0.00491

AC:

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

2.2

(source)

DANN

Benign

0.74

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over