Genetic Variant H2AC16:p.Val115Val (chr6-27865699-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003511.3(H2AC16):c.345G>T(p.Val115Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,614,236 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 60 hom. )

Consequence

H2AC16
NM_003511.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.858

Publications

2 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-27865699-G-T is Benign according to our data. Variant chr6-27865699-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656317.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.858 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003511.3. 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
	H2AC16	NM_003511.3	MANE Select	c.345G>T	p.Val115Val	synonymous	Exon 1 of 1	NP_003502.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2AC16	ENST00000613174.2	TSL:6 MANE Select	c.345G>T	p.Val115Val	synonymous	Exon 1 of 1	ENSP00000482538.2	P0C0S8

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

792

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00534

AC:

1344

AN:

251474

AF XY:

0.00554

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.00748

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00749

AC:

10943

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

5352

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00387

AC:

173

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00394

AC:

103

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00104

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0120

AC:

641

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00852

AC:

9473

AN:

1112012

Other (OTH)

AF:

0.00682

AC:

412

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

765

1530

2294

3059

3824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.00520

AC:

792

AN:

152342

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41574

American (AMR)

AF:

0.00379

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00745

AC:

507

AN:

68034

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00694

Hom.:

Bravo

AF:

0.00451

EpiCase

AF:

0.00714

EpiControl

AF:

0.00729

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.4

(source)

DANN

Benign

0.84

PhyloP100

0.86

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over