rs16891378

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

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
	H4C4	NM_003539.4	MANE Select	c.*129T>C		downstream_gene	N/A	NP_003530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291336	ENST00000707189.1		n.999+64465A>G		intron	N/A
	ENSG00000291338	ENST00000707191.1		n.1000+30515A>G		intron	N/A
	H4C4	ENST00000614247.2	TSL:6 MANE Select	c.*129T>C		downstream_gene	N/A	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

African (AFR) AF: 0.182 AC: 3020 AN: 16558

American (AMR) AF: 0.141 AC: 2866 AN: 20296

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1702 AN: 15144

East Asian (EAS) AF: 0.0789 AC: 2666 AN: 33804

South Asian (SAS) AF: 0.208 AC: 10841 AN: 52084

European-Finnish (FIN) AF: 0.165 AC: 7764 AN: 46974

Middle Eastern (MID) AF: 0.237 AC: 570 AN: 2406

European-Non Finnish (NFE) AF: 0.140 AC: 63437 AN: 451516

Other (OTH) AF: 0.146 AC: 4834 AN: 33120

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

African (AFR) AF: 0.177 AC: 7335 AN: 41528

American (AMR) AF: 0.145 AC: 2223 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5190

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1685 AN: 10614

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9693 AN: 68026

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.149 Hom.: 2322

Bravo AF: 0.152

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.54
PhyloP100		-0.34
PromoterAI		-0.058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs16891378; hg19: chr6-26188864;