dbSNP rs200981: H2AC16:p.Lys14Lys (chr6-27865396-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003511.3(H2AC16):c.42A>G(p.Lys14Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,611,568 control chromosomes in the GnomAD database, including 12,839 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 0.12 ( 1325 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11514 hom. )

Consequence

H2AC16
NM_003511.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Publications

28 publications found

Variant links:

Genes affected

H2AC16 (HGNC:4730): (H2A clustered histone 16) 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 is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

H2AC16 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=-0.69).

BP7

Synonymous conserved (PhyloP=3.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2AC16	NM_003511.3 link	c.42A>G	p.Lys14Lys	synonymous_variant	Exon 1 of 1	ENST00000613174.2	NP_003502.1	P0C0S8A4FTV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2AC16	ENST00000613174.2 link	c.42A>G	p.Lys14Lys	synonymous_variant	Exon 1 of 1	6	NM_003511.3	ENSP00000482538.2		P0C0S8

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18728

AN:

151994

Hom.:

1318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.103

AC:

25819

AN:

250236

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.0361

Gnomad EAS exome

AF:

0.0778

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0861

GnomAD4 exome

AF:

0.120

AC:

175666

AN:

1459456

Hom.:

11514

Cov.:

AF XY:

0.119

AC XY:

86245

AN XY:

725572

show subpopulations

African (AFR)

AF:

0.191

AC:

6391

AN:

33410

American (AMR)

AF:

0.117

AC:

5213

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

977

AN:

26040

East Asian (EAS)

AF:

0.0856

AC:

3394

AN:

39640

South Asian (SAS)

AF:

0.117

AC:

10084

AN:

86148

European-Finnish (FIN)

AF:

0.0535

AC:

2853

AN:

53332

Middle Eastern (MID)

AF:

0.0501

AC:

288

AN:

5752

European-Non Finnish (NFE)

AF:

0.126

AC:

139844

AN:

1110318

Other (OTH)

AF:

0.110

AC:

6622

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

11480

22960

34440

45920

57400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5398

10796

16194

21592

26990

<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:

0.123

AC:

18764

AN:

152112

Hom.:

1325

Cov.:

AF XY:

0.119

AC XY:

8869

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.184

AC:

7619

AN:

41472

American (AMR)

AF:

0.122

AC:

1868

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.0822

AC:

424

AN:

5156

South Asian (SAS)

AF:

0.110

AC:

527

AN:

4806

European-Finnish (FIN)

AF:

0.0487

AC:

516

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7337

AN:

67988

Other (OTH)

AF:

0.102

AC:

215

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

843

1686

2529

3372

4215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.259

Hom.:

7077

Bravo

AF:

0.130

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.5

(source)

DANN

Benign

0.53

PhyloP100

3.2

PromoterAI

0.16

Neutral

(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