6-26016234-C-T

Variant names:

• chr6-26016234-C-T
• rs199750

Variant summary

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

The variant allele was found at a frequency of 0.766 in 152,188 control chromosomes in the GnomAD database, including 45,443 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 0.77 (45442 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: H3P26 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

H3P26 (HGNC:4770): (H3 histone pseudogene 26) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H3P26		n.26016234C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H3P26	ENST00000437528.1	n.-145C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116459 AN: 152068 Hom.: 45398 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.766 AC: 116559 AN: 152186 Hom.: 45442 Cov.: 31 AF XY: 0.766 AC XY: 56953 AN XY: 74396

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.785

Alfa AF: 0.703 Hom.: 51336

Bravo AF: 0.776

Asia WGS AF: 0.744 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199750; hg19: chr6-26016462;