ENST00000314088.6:n.*124+365C>T

Variant names:

• chr6-26125114-C-T
• rs129128
• ENST00000314088.6:n.*124+365C>T

Variant summary

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

The ENST00000314088.6(H2AC6):​n.*124+365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,248 control chromosomes in the GnomAD database, including 62,897 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 0.91 (62897 hom., cov: 32)
• Consequence: H2AC6 ENST00000314088.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 18 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2AC6	ENST00000314088.6	n.*124+365C>T		intron_variant	Intron 1 of 1	1		ENSP00000321389.5
H2AC6	ENST00000602637.1	c.*8+481C>T		intron_variant	Intron 1 of 1	2		ENSP00000473534.1
ENSG00000291336	ENST00000707189.1	n.999+943C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 138058 AN: 152130 Hom.: 62830 Cov.: 32

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.908 AC: 138184 AN: 152248 Hom.: 62897 Cov.: 32 AF XY: 0.910 AC XY: 67733 AN XY: 74430

African (AFR) AF: 0.973 AC: 40407 AN: 41540

American (AMR) AF: 0.900 AC: 13770 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3046 AN: 3470

East Asian (EAS) AF: 0.975 AC: 5054 AN: 5184

South Asian (SAS) AF: 0.909 AC: 4392 AN: 4832

European-Finnish (FIN) AF: 0.926 AC: 9813 AN: 10596

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58726 AN: 68014

Other (OTH) AF: 0.884 AC: 1865 AN: 2110

Alfa AF: 0.875 Hom.: 108588

Bravo AF: 0.908

Asia WGS AF: 0.935 AC: 3254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.37
PhyloP100		-0.36
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: rs129128; hg19: chr6-26125342;