rs10946808

Positions:

• chr6-26233159-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000403259.1(H2AC9P):​n.38A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,582 control chromosomes in the GnomAD database, including 7,325 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 (7325 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: H2AC9P ENST00000403259.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

H2AC9P (HGNC:18805): (H2A clustered histone 9, pseudogene) Histones are basic nuclear proteins responsible for 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 histone pseudogene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Oct 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2AC9P	ENST00000403259.1	n.38A>G		non_coding_transcript_exon_variant	1/1
	ENST00000707189.1	n.999+108988A>G		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1000+75038A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40439 AN: 151460 Hom.: 7319 Cov.: 33

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.257

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.267 AC: 40455 AN: 151582 Hom.: 7325 Cov.: 33 AF XY: 0.281 AC XY: 20854 AN XY: 74114

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.261

Alfa AF: 0.300 Hom.: 17339

Bravo AF: 0.246

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10946808; hg19: chr6-26233387;