ENST00000607124.2:c.*3841G>A

Variant names:

• chr6-27122625-C-T
• rs7745603
• ENST00000607124.2:c.*3841G>A

Variant summary

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

The ENST00000607124.2(H2BC11):​c.*3841G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,882 control chromosomes in the GnomAD database, including 7,254 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 0.29 (7254 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: H2BC11 ENST00000607124.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• Publications: 29 publications found

Genes affected

H2BC11 (HGNC:4761): (H2B clustered histone 11) 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 H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the histone microcluster on chromosome 6p21.33. [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 (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607124.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC11	ENST00000607124.2	TSL:3	c.*3841G>A		downstream_gene	N/A	ENSP00000476136.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43284 AN: 151762 Hom.: 7234 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.285 AC: 43332 AN: 151880 Hom.: 7254 Cov.: 32 AF XY: 0.279 AC XY: 20728 AN XY: 74254

African (AFR) AF: 0.467 AC: 19295 AN: 41360

American (AMR) AF: 0.251 AC: 3833 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3468

East Asian (EAS) AF: 0.184 AC: 949 AN: 5168

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4810

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10530

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15304 AN: 67966

Other (OTH) AF: 0.269 AC: 568 AN: 2114

Alfa AF: 0.240 Hom.: 17387

Bravo AF: 0.301

Asia WGS AF: 0.194 AC: 674 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	0.57
DANN	Benign	0.27
PhyloP100		-0.77

Splicing

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

Other links and lift over

dbSNP: rs7745603; hg19: chr6-27090404;