6-26086974-G-C

Position:

• chr6-26086974-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_144383.1(HFE-AS1):​n.1501C>G 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 0.373 in 152,024 control chromosomes in the GnomAD database, including 11,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.37 (11359 hom., cov: 32)
• Consequence: HFE-AS1 NR_144383.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

Genes affected

HFE-AS1 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-26086974-G-C is Benign according to our data. Variant chr6-26086974-G-C is described in ClinVar as [Benign]. Clinvar id is 1168055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HFE-AS1	NR_144383.1	n.1501C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC4	ENST00000707188.1	c.*1510C>G		3_prime_UTR_variant, NMD_transcript_variant	3/3			ENSP00000516775

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56614 AN: 151906 Hom.: 11356 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.373 AC: 56633 AN: 152024 Hom.: 11359 Cov.: 32 AF XY: 0.377 AC XY: 28018 AN XY: 74292

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.383

Alfa AF: 0.300 Hom.: 988

Bravo AF: 0.367

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary hemochromatosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

This variant is associated with the following publications: (PMID: 21412944) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2794720; hg19: chr6-26087202;