6-26246436-C-T

Variant names:

• chr6-26246436-C-T
• rs6913828
• ENST00000707189.1:n.999+122265C>T

Variant summary

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

The ENST00000707189.1(ENSG00000291336):​n.999+122265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,204 control chromosomes in the GnomAD database, including 1,198 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 0.10 (1198 hom., cov: 32)
• Consequence: ENSG00000291336 ENST00000707189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 6 publications found

Genes affected

ENSG00000291336 (HGNC:):

H4C7 (HGNC:4792): (H4 clustered histone 7) 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 H4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000707189.1. 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
	H4C7	NM_003547.3	MANE Select	c.*245G>A		downstream_gene	N/A	NP_003538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291336	ENST00000707189.1		n.999+122265C>T		intron	N/A
	ENSG00000291338	ENST00000707191.1		n.1000+88315C>T		intron	N/A
	H4C7	ENST00000611444.2	TSL:6 MANE Select	c.*245G>A		downstream_gene	N/A	ENSP00000477870.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15487 AN: 152086 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.102 AC: 15490 AN: 152204 Hom.: 1198 Cov.: 32 AF XY: 0.0998 AC XY: 7424 AN XY: 74422

African (AFR) AF: 0.222 AC: 9204 AN: 41492

American (AMR) AF: 0.0890 AC: 1360 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3472

East Asian (EAS) AF: 0.0652 AC: 338 AN: 5186

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4828

European-Finnish (FIN) AF: 0.0422 AC: 448 AN: 10612

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3375 AN: 68014

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0615 Hom.: 1289

Bravo AF: 0.112

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs6913828; hg19: chr6-26246664;