6-26133388-A-G

Position:

• chr6-26133388-A-G

Variant summary

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

The ENST00000314088.6(H2AC6):​c.*125-4666A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,954 control chromosomes in the GnomAD database, including 27,305 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 0.59 (27305 hom., cov: 31)
• Consequence: H2AC6 ENST00000314088.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

Genes affected

H2AC6 (HGNC:4733): (H2A clustered histone 6) 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 large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H2AC6	ENST00000314088.6	c.*125-4666A>G		intron_variant, NMD_transcript_variant		1
	ENST00000707189.1	n.999+9217A>G		intron_variant, non_coding_transcript_variant
H2AC6	ENST00000602637.1	c.*9-4666A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89698 AN: 151836 Hom.: 27279 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.591 AC: 89770 AN: 151954 Hom.: 27305 Cov.: 31 AF XY: 0.599 AC XY: 44463 AN XY: 74290

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.563

Alfa AF: 0.591 Hom.: 32130

Bravo AF: 0.577

Asia WGS AF: 0.721 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.52

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: rs198806; hg19: chr6-26133616;