rs1800708

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

17 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000410.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HFE	NM_000410.4	MANE Select	c.893-44T>C	intron	N/A	NP_000401.1	Q30201-1
HFE	NM_001384164.1		c.893-44T>C	intron	N/A	NP_001371093.1	H7C4K4
HFE	NM_001406751.1		c.884-44T>C	intron	N/A	NP_001393680.1	Q6B0J5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HFE	ENST00000357618.10	TSL:1 MANE Select	c.893-44T>C	intron	N/A	ENSP00000417404.1	Q30201-1
HFE	ENST00000470149.5	TSL:1	c.884-44T>C	intron	N/A	ENSP00000419725.1	Q6B0J5
HFE	ENST00000461397.6	TSL:1	c.851-44T>C	intron	N/A	ENSP00000420802.1	Q30201-3

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

GnomAD2 exomes

AF:

0.155

AC:

38973

AN:

251106

AF XY:

0.151

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 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

African (AFR)

AF:

0.0917

AC:

3068

AN:

33452

American (AMR)

AF:

0.231

AC:

10344

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

2055

AN:

26124

East Asian (EAS)

AF:

0.622

AC:

24678

AN:

39692

South Asian (SAS)

AF:

0.186

AC:

16001

AN:

86226

European-Finnish (FIN)

AF:

0.198

AC:

10550

AN:

53406

Middle Eastern (MID)

AF:

0.0984

AC:

567

AN:

5762

European-Non Finnish (NFE)

AF:

0.0594

AC:

66031

AN:

1111252

Other (OTH)

AF:

0.107

AC:

6439

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7284

14568

21853

29137

36421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2824

5648

8472

11296

14120

<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:

0.115

AC:

17471

AN:

152138

Hom.:

1789

Cov.:

AF XY:

0.127

AC XY:

9432

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0956

AC:

3966

AN:

41496

American (AMR)

AF:

0.174

AC:

2657

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

249

AN:

3470

East Asian (EAS)

AF:

0.560

AC:

2887

AN:

5158

South Asian (SAS)

AF:

0.197

AC:

950

AN:

4822

European-Finnish (FIN)

AF:

0.201

AC:

2132

AN:

10584

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0630

AC:

4283

AN:

68012

Other (OTH)

AF:

0.132

AC:

278

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

728

1456

2184

2912

3640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.0837

Hom.:

1327

Bravo

AF:

0.114

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

(source)

DANN

Benign

0.62

PhyloP100

0.22

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over