rs200981

Positions:

• chr6-27865396-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
H2AC16	NM_003511.3	c.42A>G	p.Lys14Lys	synonymous_variant	1/1	ENST00000613174.2	NP_003502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2AC16	ENST00000613174.2	c.42A>G	p.Lys14Lys	synonymous_variant	1/1	6	NM_003511.3	ENSP00000482538.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18728 AN: 151994 Hom.: 1318 Cov.: 32

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

GnomAD3 exomes AF: 0.103 AC: 25819 AN: 250236 Hom.: 1590 AF XY: 0.102 AC XY: 13850 AN XY: 135310

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 SAS exome AF: 0.117

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.: 32 AF XY: 0.119 AC XY: 86245 AN XY: 725572

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.123 AC: 18764 AN: 152112 Hom.: 1325 Cov.: 32 AF XY: 0.119 AC XY: 8869 AN XY: 74364

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.102

Alfa AF: 0.110 Hom.: 444

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
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs200981; hg19: chr6-27833174;