chr1-228458140-C-G

Variant names:

• chr1-228458140-C-G
• NM_175055.3:c.11C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175055.3(H2BC26):​c.11C>G​(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: H2BC26 NM_175055.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

Genes affected

H2BC26 (HGNC:20514): (H2B clustered histone 26) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone 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 is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene contain a palindromic termination element. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3067588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2BC26	NM_175055.3	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 1	ENST00000693095.1	NP_778225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC26	ENST00000693095.1	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 1		NM_175055.3	ENSP00000509901.1
H2BC26	ENST00000620438.2	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 1	6		ENSP00000479284.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1452904 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.013	D
Polyphen		0.0060	B
Vest4		0.53
MutPred		0.29		Gain of MoRF binding (P = 1e-04);
MVP		0.49
ClinPred		0.83	D
GERP RS		3.0
Varity_R		0.18
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-228645841;