chr1-149886415-C-G

Variant names:

• chr1-149886415-C-G
• NM_003528.3:c.226G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003528.3(H2BC21):​c.226G>C​(p.Gly76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: H2BC21 NM_003528.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

H2BC21 (HGNC:4760): (H2B clustered histone 21) 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 encodes a replication-dependent histone that is a member of the histone H2B family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif. The protein has antibacterial and antifungal antimicrobial activity. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003528.3. 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
	H2BC21	NM_003528.3	MANE Select	c.226G>C	p.Gly76Arg	missense	Exon 1 of 1	NP_003519.1	Q16778

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC21	ENST00000369155.4	TSL:6 MANE Select	c.226G>C	p.Gly76Arg	missense	Exon 1 of 1	ENSP00000358151.2	Q16778

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.019	D
Sift4G	Benign	0.11	T
Polyphen		0.93	P
Vest4		0.43
MutPred		0.23		Gain of MoRF binding (P = 0.0069)
MVP		0.84
MPC		1.9
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		0.79
Mutation Taster		=83/17	polymorphism

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

hg19: chr1-149857965;