Genetic Variant H2AC6:n.*124+365C>T (chr6-26125114-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000602637.1(H2AC6):c.*8+481C>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
ENST00000602637.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Publications

18 publications found

Variant links:

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

H2AC6 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
H2AC6	ENST00000314088.6	TSL:1	n.*124+365C>T	intron	N/A	ENSP00000321389.5	Q93077
H2AC6	ENST00000602637.1	TSL:2	c.*8+481C>T	intron	N/A	ENSP00000473534.1	Q93077
ENSG00000291336	ENST00000707189.1		n.999+943C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

138058

AN:

152130

Hom.:

62830

Cov.:

show subpopulations

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.:

AF XY:

0.910

AC XY:

67733

AN XY:

74430

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

660

1319

1979

2638

3298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.9

(source)

DANN

Benign

0.37

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over