6-26114474-C-T

Variant names:

• chr6-26114474-C-T
• rs13161
• NM_001381989.1:c.*671G>A

Variant summary

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

The NM_001381989.1(H2BC4):​c.*671G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,834 control chromosomes in the GnomAD database, including 17,733 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 0.47 (17733 hom., cov: 32)
• Consequence: H2BC4 NM_001381989.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 15 publications found

Genes affected

H2BC4 (HGNC:4757): (H2B 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. The protein has antibacterial and antifungal antimicrobial activity. The main transcript variant of this gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. This transcript variant lacks a polyA tail but instead contains a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Apr 2020]

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 (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2BC4	NM_001381989.1	c.*671G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000707188.1	n.*9+9041G>A		intron_variant	Intron 1 of 2			ENSP00000516775.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72026 AN: 151716 Hom.: 17721 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.475 AC: 72076 AN: 151834 Hom.: 17733 Cov.: 32 AF XY: 0.471 AC XY: 34916 AN XY: 74202

African (AFR) AF: 0.385 AC: 15921 AN: 41404

American (AMR) AF: 0.447 AC: 6831 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1474 AN: 5150

South Asian (SAS) AF: 0.426 AC: 2045 AN: 4804

European-Finnish (FIN) AF: 0.552 AC: 5810 AN: 10530

Middle Eastern (MID) AF: 0.421 AC: 122 AN: 290

European-Non Finnish (NFE) AF: 0.542 AC: 36832 AN: 67906

Other (OTH) AF: 0.425 AC: 895 AN: 2106

Alfa AF: 0.502 Hom.: 29031

Bravo AF: 0.461

Asia WGS AF: 0.411 AC: 1422 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		0.022

Splicing

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

Other links and lift over

dbSNP: rs13161; hg19: chr6-26114702;