rs104894517

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005143.5(HP):ā€‹c.740T>Cā€‹(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: š‘“ 0.00026 ( 0 hom., cov: 31)
Exomes š‘“: 0.000049 ( 0 hom. )

Consequence

HP
NM_005143.5 missense

Scores

12
4
3

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 6.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HPNM_005143.5 linkuse as main transcriptc.740T>C p.Ile247Thr missense_variant 7/7 ENST00000355906.10 NP_005134.1 P00738-1Q6PEJ8
HPNM_001126102.3 linkuse as main transcriptc.563T>C p.Ile188Thr missense_variant 5/5 NP_001119574.1 P00738-2Q6PEJ8
HPNM_001318138.2 linkuse as main transcriptc.563T>C p.Ile188Thr missense_variant 5/5 NP_001305067.1 P00738Q6PEJ8A0A0C4DGL8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HPENST00000355906.10 linkuse as main transcriptc.740T>C p.Ile247Thr missense_variant 7/71 NM_005143.5 ENSP00000348170.5 P00738-1
TXNL4BENST00000562153.5 linkuse as main transcriptc.285-16052A>G intron_variant 4 ENSP00000454635.2 H3BN11

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152208
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.0000802
AC:
20
AN:
249424
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135324
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000486
AC:
71
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00125
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152326
Hom.:
0
Cov.:
31
AF XY:
0.000215
AC XY:
16
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000794
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000516
Hom.:
0
Bravo
AF:
0.000366
ESP6500AA
AF:
0.000527
AC:
2
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.000108
AC:
13
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Anhaptoglobinemia Other:1
Affects, no assertion criteria providedliterature onlyOMIMApr 01, 2004- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.51
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Pathogenic
0.96
.;D;T;.;.;.;T;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;D;D;D;D;D;.;D
M_CAP
Pathogenic
0.64
D
MetaRNN
Pathogenic
0.79
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.4
.;M;.;.;.;.;.;.
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-4.2
D;D;.;D;D;.;.;D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D;D;.;D;D;.;.;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;.;.;.;.
Vest4
0.89
MVP
0.98
MPC
0.92
ClinPred
0.59
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.90
gMVP
0.90

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

LitVar

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

Other links and lift over

dbSNP: rs104894517; hg19: chr16-72094308; API