rs1572982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000410.4(HFE):c.1007-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,580,402 control chromosomes in the GnomAD database, including 198,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21637 hom., cov: 31)

Exomes 𝑓: 0.49 ( 176664 hom. )

Consequence

HFE
NM_000410.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.29

Publications

39 publications found

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:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 6-26094139-G-A is Benign according to our data. Variant chr6-26094139-G-A is described in ClinVar as Benign. ClinVar VariationId is 1164200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HFE	NM_000410.4 link	c.1007-47G>A		intron_variant	Intron 5 of 5	ENST00000357618.10	NP_000401.1	Q30201-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HFE	ENST00000357618.10 link	c.1007-47G>A		intron_variant	Intron 5 of 5	1	NM_000410.4	ENSP00000417404.1		Q30201-1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79838

AN:

151786

Hom.:

21616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.518

AC:

129403

AN:

249668

AF XY:

0.520

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.492

AC:

703130

AN:

1428498

Hom.:

176664

Cov.:

AF XY:

0.495

AC XY:

352461

AN XY:

712736

show subpopulations

African (AFR)

AF:

0.624

AC:

20450

AN:

32796

American (AMR)

AF:

0.544

AC:

24327

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

15020

AN:

25940

East Asian (EAS)

AF:

0.789

AC:

31219

AN:

39572

South Asian (SAS)

AF:

0.583

AC:

49909

AN:

85564

European-Finnish (FIN)

AF:

0.456

AC:

24266

AN:

53184

Middle Eastern (MID)

AF:

0.626

AC:

3157

AN:

5042

European-Non Finnish (NFE)

AF:

0.466

AC:

504592

AN:

1082538

Other (OTH)

AF:

0.510

AC:

30190

AN:

59182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

18331

36662

54993

73324

91655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15214

30428

45642

60856

76070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.526

AC:

79906

AN:

151904

Hom.:

21637

Cov.:

AF XY:

0.530

AC XY:

39371

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.616

AC:

25509

AN:

41430

American (AMR)

AF:

0.553

AC:

8451

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1961

AN:

3468

East Asian (EAS)

AF:

0.712

AC:

3674

AN:

5158

South Asian (SAS)

AF:

0.575

AC:

2768

AN:

4818

European-Finnish (FIN)

AF:

0.451

AC:

4754

AN:

10532

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31135

AN:

67916

Other (OTH)

AF:

0.575

AC:

1209

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1900

3801

5701

7602

9502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.481

Hom.:

38663

Bravo

AF:

0.539

Asia WGS

AF:

0.588

AC:

2046

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary hemochromatosis

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hemochromatosis type 1

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0040

(source)

DANN

Benign

0.59

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over