chr6-26045930-T-C

Variant names:

• chr6-26045930-T-C
• rs11755492
• ENST00000760529.1:n.232+156A>G

Variant summary

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

The ENST00000760529.1(ENSG00000299111):​n.232+156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,070,730 control chromosomes in the GnomAD database, including 10,814 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 0.11 (1139 hom., cov: 33)
  • Exomes 𝑓: 0.14 (9675 hom.)
• Consequence: ENSG00000299111 ENST00000760529.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 12 publications found

Genes affected

ENSG00000299111 (HGNC:):

H3C3 (HGNC:4768): (H3 clustered histone 3) 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 H3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000760529.1. 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
	H3C3	NM_003531.3	MANE Select	c.*109T>C		downstream_gene	N/A	NP_003522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000299111	ENST00000760529.1		n.232+156A>G		intron	N/A
	ENSG00000299111	ENST00000760530.1		n.100+269A>G		intron	N/A
	H3C3	ENST00000612966.3	TSL:6 MANE Select	c.*109T>C		downstream_gene	N/A	ENSP00000484658.2	P68431

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16774 AN: 152056 Hom.: 1139 Cov.: 33

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.139 AC: 127889 AN: 918556 Hom.: 9675 AF XY: 0.142 AC XY: 66277 AN XY: 466184

African (AFR) AF: 0.0370 AC: 783 AN: 21148

American (AMR) AF: 0.105 AC: 2455 AN: 23298

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 4456 AN: 19402

East Asian (EAS) AF: 0.0778 AC: 2680 AN: 34440

South Asian (SAS) AF: 0.202 AC: 12648 AN: 62716

European-Finnish (FIN) AF: 0.106 AC: 3671 AN: 34690

Middle Eastern (MID) AF: 0.187 AC: 832 AN: 4440

European-Non Finnish (NFE) AF: 0.139 AC: 94239 AN: 676310

Other (OTH) AF: 0.145 AC: 6125 AN: 42112

GnomAD4 genome AF: 0.110 AC: 16770 AN: 152174 Hom.: 1139 Cov.: 33 AF XY: 0.111 AC XY: 8244 AN XY: 74396

African (AFR) AF: 0.0450 AC: 1866 AN: 41508

American (AMR) AF: 0.114 AC: 1743 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3470

East Asian (EAS) AF: 0.0834 AC: 432 AN: 5182

South Asian (SAS) AF: 0.200 AC: 961 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10582

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9411 AN: 68008

Other (OTH) AF: 0.132 AC: 278 AN: 2112

Alfa AF: 0.128 Hom.: 1947

Bravo AF: 0.106

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.22
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11755492; hg19: chr6-26046158;