6-27891675-T-C

Position:

• chr6-27891675-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

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 (AFR) allele frequency at 95% confidence interval = 0.427 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
H3C12	ENST00000479986.1	n.347-865A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.244

Alfa AF: 0.224 Hom.: 3033

Bravo AF: 0.279

Asia WGS AF: 0.216 AC: 751 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	0.41
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200969; hg19: chr6-27859453;