dbSNP rs12206204: H2BC4:c.*10-1619G>A (chr6-26116754-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000314332.5(H2BC4):c.*10-1619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,264 control chromosomes in the GnomAD database, including 23 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 0.012 ( 23 hom., cov: 32)

Consequence

H2BC4
ENST00000314332.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.498

Publications

13 publications found

Variant links:

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]

H2BC4 links:

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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=-0.85).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0115 (1755/152264) while in subpopulation SAS AF = 0.0243 (117/4812). AF 95% confidence interval is 0.0207. There are 23 homozygotes in GnomAd4. There are 829 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2BC4	NM_001381989.1 link	c.*10-1619G>A		intron_variant	Intron 1 of 1		NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000314332.5 link	c.*10-1619G>A		intron_variant	Intron 1 of 1	1		ENSP00000321744.4		P62807
H2BC4	ENST00000707188.1 link	n.*9+6761G>A		intron_variant	Intron 1 of 2			ENSP00000516775.1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1756

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00661

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0245

Gnomad FIN

AF:

0.00744

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.00861

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

GnomAD4 genome

AF:

0.0115

AC:

1755

AN:

152264

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

829

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41554

American (AMR)

AF:

0.0112

AC:

171

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0243

AC:

117

AN:

4812

European-Finnish (FIN)

AF:

0.00744

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0178

AC:

1210

AN:

68024

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0147

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

(source)

DANN

Benign

0.67

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over