ENST00000479986.1:n.347-865A>G

Variant names:

• chr6-27891675-T-C
• rs200969
• ENST00000479986.1:n.347-865A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479986.1(H3C12):​n.347-865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,092 control chromosomes in the GnomAD database, including 6,348 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 (6348 hom., cov: 32)
• Consequence: H3C12 ENST00000479986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 16 publications found

Genes affected

H3C12 (HGNC:4774): (H3 clustered histone 12) 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 H3 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]

ENSG00000305786 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479986.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3C12	ENST00000479986.1	TSL:2	n.347-865A>G		intron	N/A
	ENSG00000305786	ENST00000812940.1		n.195-3587A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40423 AN: 151974 Hom.: 6316 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40512 AN: 152092 Hom.: 6348 Cov.: 32 AF XY: 0.261 AC XY: 19423 AN XY: 74354

African (AFR) AF: 0.432 AC: 17921 AN: 41462

American (AMR) AF: 0.237 AC: 3624 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.144 AC: 743 AN: 5168

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1668 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14105 AN: 67984

Other (OTH) AF: 0.244 AC: 516 AN: 2112

Alfa AF: 0.225 Hom.: 3630

Bravo AF: 0.279

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs200969; hg19: chr6-27859453;