6-26133388-A-G

Variant names:

• chr6-26133388-A-G
• rs198806
• ENST00000314088.6:n.*125-4666A>G

Variant summary

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

The ENST00000314088.6(H2AC6):​n.*125-4666A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 26 publications found

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]

H2AC6 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314088.6. 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
	H2AC6	ENST00000314088.6	TSL:1	n.*125-4666A>G		intron	N/A	ENSP00000321389.5
	H2AC6	ENST00000602637.1	TSL:2	c.*9-4666A>G		intron	N/A	ENSP00000473534.1
	ENSG00000291336	ENST00000707189.1		n.999+9217A>G		intron	N/A

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

African (AFR) AF: 0.481 AC: 19918 AN: 41430

American (AMR) AF: 0.627 AC: 9563 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3466

East Asian (EAS) AF: 0.849 AC: 4392 AN: 5172

South Asian (SAS) AF: 0.614 AC: 2959 AN: 4822

European-Finnish (FIN) AF: 0.753 AC: 7954 AN: 10562

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41215 AN: 67936

Other (OTH) AF: 0.563 AC: 1185 AN: 2106

Alfa AF: 0.588 Hom.: 55498

Bravo AF: 0.577

Asia WGS AF: 0.721 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.52
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs198806; hg19: chr6-26133616;