Genetic Variant H2BC1:p.Ser66Ser (chr6-25727106-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
H2BC1	NM_170610.3 link	c.198C>T	p.Ser66Ser	synonymous_variant	Exon 1 of 1	ENST00000274764.5	NP_733759.1
SLC17A1	XM_017011201.3 link	c.*3-3313G>A		intron_variant	Intron 12 of 12		XP_016866690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC1	ENST00000274764.5 link	c.198C>T	p.Ser66Ser	synonymous_variant	Exon 1 of 1	6	NM_170610.3	ENSP00000274764.3
ENSG00000290217	ENST00000703602.1 link	c.*50+8235C>T		intron_variant	Intron 11 of 11			ENSP00000515390.1

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

GnomAD2 exomes

AF:

0.340

AC:

85337

AN:

251360

AF XY:

0.331

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 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

African (AFR)

AF:

0.123

AC:

4112

AN:

33478

American (AMR)

AF:

0.471

AC:

21053

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4238

AN:

26136

East Asian (EAS)

AF:

0.714

AC:

28345

AN:

39698

South Asian (SAS)

AF:

0.302

AC:

26021

AN:

86252

European-Finnish (FIN)

AF:

0.410

AC:

21892

AN:

53408

Middle Eastern (MID)

AF:

0.183

AC:

1055

AN:

5768

European-Non Finnish (NFE)

AF:

0.285

AC:

316606

AN:

1111904

Other (OTH)

AF:

0.302

AC:

18229

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16262

32523

48785

65046

81308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10724

21448

32172

42896

53620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.272

AC:

41439

AN:

152204

Hom.:

6836

Cov.:

AF XY:

0.280

AC XY:

20825

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.134

AC:

5587

AN:

41546

American (AMR)

AF:

0.364

AC:

5572

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

533

AN:

3472

East Asian (EAS)

AF:

0.693

AC:

3578

AN:

5166

South Asian (SAS)

AF:

0.315

AC:

1523

AN:

4830

European-Finnish (FIN)

AF:

0.417

AC:

4408

AN:

10568

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19380

AN:

68016

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1465

2929

4394

5858

7323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.267

Hom.:

9959

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

(source)

DANN

Benign

0.79

PhyloP100

-6.0

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over