Variant 6-26093075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000410.4(HFE):c.893-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 1,613,128 control chromosomes in the GnomAD database, including 16,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1789 hom., cov: 31)

Exomes 𝑓: 0.096 ( 14548 hom. )

Consequence

HFE
NM_000410.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.217

Variant links:

Genes affected

HFE (HGNC:4886): (homeostatic iron regulator) The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. [provided by RefSeq, May 2022]

HFE links:

HFE (HGNC:):

HFE links:

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]

H2BC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-26093075-T-C is Benign according to our data. Variant chr6-26093075-T-C is described in ClinVar as [Benign]. Clinvar id is 1236293.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HFE	NM_000410.4 linkuse as main transcript	c.893-44T>C		intron_variant		ENST00000357618.10	NP_000401.1	Q30201-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HFE	ENST00000357618.10 linkuse as main transcript	c.893-44T>C		intron_variant		1	NM_000410.4	ENSP00000417404.1		Q30201-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17448

AN:

152020

Hom.:

1783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0956

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.155

AC:

38973

AN:

251106

Hom.:

5417

AF XY:

0.151

AC XY:

20472

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0937

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.0806

Gnomad EAS exome

AF:

0.566

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.0638

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.0956

AC:

139733

AN:

1460990

Hom.:

14548

Cov.:

AF XY:

0.0980

AC XY:

71201

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0917

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.0787

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.0594

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.115

AC:

17471

AN:

152138

Hom.:

1789

Cov.:

AF XY:

0.127

AC XY:

9432

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0956

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.0718

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.0630

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.0773

Hom.:

654

Bravo

AF:

0.114

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over