rs198820

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-26124015-G-A
• chr6-26124015-G-T

Variant summary

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

The ENST00000707189.1(ENSG00000291336):​n.843G>A 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 0.347 in 1,450,462 control chromosomes in the GnomAD database, including 90,987 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 (7334 hom., cov: 32)
  • Exomes 𝑓: 0.35 (83653 hom.)
• Consequence: ENSG00000291336 ENST00000707189.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43699 AN: 151948 Hom.: 7332 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.353 AC: 458968 AN: 1298396 Hom.: 83653 Cov.: 21 AF XY: 0.354 AC XY: 227499 AN XY: 643120

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.287 AC: 43719 AN: 152066 Hom.: 7334 Cov.: 32 AF XY: 0.286 AC XY: 21254 AN XY: 74328

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.258

Alfa AF: 0.311 Hom.: 761

Bravo AF: 0.274

Asia WGS AF: 0.270 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.6
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs198820; hg19: chr6-26124243; COSMIC: COSV58415959;