Variant 6-25727106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_170610.3(H2BC1):c.198C>T(p.Ser66Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,964 control chromosomes in the GnomAD database, including 80,186 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 0.27 ( 6836 hom., cov: 32)

Exomes 𝑓: 0.30 ( 73350 hom. )

Consequence

H2BC1
NM_170610.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.97

Variant links:

Genes affected

H2BC1 (HGNC:18730): (H2B clustered histone 1) 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 testis/sperm-specific member of the histone H2B family. Transcripts from this gene contain a palindromic termination element. [provided by RefSeq, Aug 2015]

H2BC1 links:

ENSG00000290217 (HGNC:):

ENSG00000290217 links:

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=-5.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2BC1	NM_170610.3 link	c.198C>T	p.Ser66Ser	synonymous_variant	1/1	ENST00000274764.5	NP_733759.1	Q96A08
SLC17A1	XM_017011201.3 link	c.*3-3313G>A		intron_variant			XP_016866690.2	Q14916-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC1	ENST00000274764.5 link	c.198C>T	p.Ser66Ser	synonymous_variant	1/1	6	NM_170610.3	ENSP00000274764.3		Q96A08
ENSG00000290217	ENST00000703602.1 link	c.*50+8235C>T		intron_variant				ENSP00000515390.1		A0A994J4C2

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41390

AN:

152086

Hom.:

6818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.340

AC:

85337

AN:

251360

Hom.:

17295

AF XY:

0.331

AC XY:

44967

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.708

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.302

AC:

441551

AN:

1461760

Hom.:

73350

Cov.:

AF XY:

0.301

AC XY:

218869

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.272

AC:

41439

AN:

152204

Hom.:

6836

Cov.:

AF XY:

0.280

AC XY:

20825

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.417

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.268

Hom.:

8180

Bravo

AF:

0.265

Asia WGS

AF:

0.464

AC:

1612

AN:

3478

EpiCase

AF:

0.267

EpiControl

AF:

0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0020

DANN

Benign

0.79

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over