rs16891378

Variant names:

• chr6-26188636-A-G
• rs16891378
• ENST00000707189.1:n.999+64465A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707189.1(ENSG00000291336):​n.999+64465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 824,180 control chromosomes in the GnomAD database, including 9,487 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 0.15 (1907 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7580 hom.)
• Consequence: ENSG00000291336 ENST00000707189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

ENSG00000291336 (HGNC:):

H4C4 (HGNC:4782): (H4 clustered histone 4) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H4C4	NM_003539.4	c.*129T>C		downstream_gene_variant		ENST00000614247.2	NP_003530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291336	ENST00000707189.1	n.999+64465A>G		intron_variant	Intron 1 of 1
ENSG00000291338	ENST00000707191.1	n.1000+30515A>G		intron_variant	Intron 1 of 1
H4C4	ENST00000614247.2	c.*129T>C		downstream_gene_variant		6	NM_003539.4	ENSP00000479461.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23435 AN: 152160 Hom.: 1910 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.145 AC: 97700 AN: 671902 Hom.: 7580 AF XY: 0.149 AC XY: 51338 AN XY: 345338

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0789

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.154 AC: 23440 AN: 152278 Hom.: 1907 Cov.: 32 AF XY: 0.155 AC XY: 11537 AN XY: 74450

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.166

Alfa AF: 0.147 Hom.: 1719

Bravo AF: 0.152

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16891378; hg19: chr6-26188864;