rs104894517

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005143.5(HP):c.740T>C(p.Ile247Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000681 in 1,614,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

HP
NM_005143.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 6.50

Publications

1 publications found

Variant links:

Genes affected

HP (HGNC:5141): (haptoglobin) This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

HP links:

ENSG00000310525 (HGNC:):

ENSG00000310525 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.791

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005143.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HP	NM_005143.5	MANE Select	c.740T>C	p.Ile247Thr	missense	Exon 7 of 7	NP_005134.1	P00738-1
HP	NM_001126102.3		c.563T>C	p.Ile188Thr	missense	Exon 5 of 5	NP_001119574.1	P00738-2
HP	NM_001318138.2		c.563T>C	p.Ile188Thr	missense	Exon 5 of 5	NP_001305067.1	A0A0C4DGL8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HP	ENST00000355906.10	TSL:1 MANE Select	c.740T>C	p.Ile247Thr	missense	Exon 7 of 7	ENSP00000348170.5	P00738-1
HP	ENST00000398131.6	TSL:1	c.563T>C	p.Ile188Thr	missense	Exon 5 of 5	ENSP00000381199.2	P00738-2
HP	ENST00000565574.5	TSL:1	c.563T>C	p.Ile188Thr	missense	Exon 5 of 5	ENSP00000454966.1	A0A0C4DGL8

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000802

AC:

AN:

249424

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1112006

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000256

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41586

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000364

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.000527

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000108

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Affects

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Anhaptoglobinemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.51

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Pathogenic

0.96

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.64

MetaRNN

Pathogenic

0.79

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.4

PhyloP100

6.5

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.89

MVP

0.98

MPC

0.92

ClinPred

0.59

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.90

gMVP

0.90

Mutation Taster

=2/98

disease causing

(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

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