6-26124015-G-T

Variant names:

• chr6-26124015-G-T
• rs198820
• ENST00000707189.1:n.843G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000707189.1(ENSG00000291336):​n.843G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 1,300,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: ENSG00000291336 ENST00000707189.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

Genes affected

ENSG00000291336 (HGNC:):

H2AC6 (HGNC:4733): (H2A clustered histone 6) 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 H2A 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]

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2AC6	NM_003512.4	c.-218G>T		upstream_gene_variant		ENST00000377791.4	NP_003503.1
H2BC4	NM_003526.3	c.-111C>A		upstream_gene_variant		ENST00000396984.2	NP_003517.2
H2BC4	NM_001381989.1	c.-111C>A		upstream_gene_variant			NP_001368918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H2AC6	ENST00000377791.4	c.-218G>T		upstream_gene_variant		1	NM_003512.4	ENSP00000367022.2
H2BC4	ENST00000396984.2	c.-111C>A		upstream_gene_variant		6	NM_003526.3	ENSP00000380180.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000231 AC: 3 AN: 1300558 Hom.: 0 Cov.: 21 AF XY: 0.00000310 AC XY: 2 AN XY: 644156

African (AFR) AF: 0.00 AC: 0 AN: 28858

American (AMR) AF: 0.00 AC: 0 AN: 28588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20102

East Asian (EAS) AF: 0.00 AC: 0 AN: 38766

South Asian (SAS) AF: 0.00 AC: 0 AN: 70612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5034

European-Non Finnish (NFE) AF: 0.00000199 AC: 2 AN: 1004398

Other (OTH) AF: 0.0000184 AC: 1 AN: 54242

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-1.9
PromoterAI		-0.073	Neutral

Splicing

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

Other links and lift over

dbSNP: rs198820; hg19: chr6-26124243;