rs198820

Variant names:

• chr6-26124015-G-A
• rs198820
• ENST00000904682.1:c.-111C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000904682.1(H2BC4):​c.-111C>T variant causes a 5 prime UTR 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: H2BC4 ENST00000904682.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 14 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]

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]

H2AC6 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000904682.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2AC6	NM_003512.4	MANE Select	c.-218G>A		upstream_gene	N/A	NP_003503.1	Q93077
	H2BC4	NM_003526.3	MANE Select	c.-111C>T		upstream_gene	N/A	NP_003517.2
	H2BC4	NM_001381989.1		c.-111C>T		upstream_gene	N/A	NP_001368918.1	P62807

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H2BC4	ENST00000904682.1		c.-111C>T		5_prime_UTR	Exon 1 of 2	ENSP00000574741.1
	ENSG00000291336	ENST00000707189.1		n.843G>A		non_coding_transcript_exon	Exon 1 of 2
	H2AC6	ENST00000377791.4	TSL:1 MANE Select	c.-218G>A		upstream_gene	N/A	ENSP00000367022.2	Q93077

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

African (AFR) AF: 0.104 AC: 3014 AN: 28848

American (AMR) AF: 0.329 AC: 9401 AN: 28554

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 5909 AN: 20084

East Asian (EAS) AF: 0.108 AC: 4184 AN: 38760

South Asian (SAS) AF: 0.336 AC: 23681 AN: 70534

European-Finnish (FIN) AF: 0.367 AC: 18332 AN: 49914

Middle Eastern (MID) AF: 0.281 AC: 1415 AN: 5032

European-Non Finnish (NFE) AF: 0.374 AC: 374847 AN: 1002500

Other (OTH) AF: 0.336 AC: 18185 AN: 54170

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

African (AFR) AF: 0.119 AC: 4938 AN: 41504

American (AMR) AF: 0.312 AC: 4761 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3472

East Asian (EAS) AF: 0.138 AC: 715 AN: 5176

South Asian (SAS) AF: 0.346 AC: 1662 AN: 4810

European-Finnish (FIN) AF: 0.361 AC: 3811 AN: 10568

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25776 AN: 67946

Other (OTH) AF: 0.258 AC: 544 AN: 2106

Alfa AF: 0.342 Hom.: 15946

Bravo AF: 0.274

Asia WGS AF: 0.270 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-1.9
PromoterAI		-0.042	Neutral
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV58415959;