Variant 1-149812179-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001024599.5(H2BC18):c.145G>A(p.Val49Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

H2BC18
NM_001024599.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

Variant links:

Genes affected

H2BC18 (HGNC:24700): (H2B clustered histone 18) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

H2BC18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2BC18	NM_001024599.5 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	1/1	ENST00000369167.3	NP_001019770.1
H2BC18	NM_001161334.2 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	1/2		NP_001154806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC18	ENST00000369167.3 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	1/1		NM_001024599.5	ENSP00000358164	P1	Q5QNW6-1
H2BC18	ENST00000469483.1 linkuse as main transcript	n.160G>A		non_coding_transcript_exon_variant	1/2	1
H2BC18	ENST00000545683.1 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	1/2	2		ENSP00000445831		Q5QNW6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251450

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.145G>A (p.V49I) alteration is located in exon 1 (coding exon 1) of the HIST2H2BF gene. This alteration results from a G to A substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

0.059

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.93

N;N

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.11

T;T

Polyphen

1.0

.;D

Vest4

0.62

MutPred

0.64

Gain of catalytic residue at P51 (P = 0.0281);Gain of catalytic residue at P51 (P = 0.0281);

MVP

0.89

MPC

2.6

ClinPred

0.79

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.61

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over