rs104894517
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005143.5(HP):āc.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
NM_005143.5 missense
Scores
12
4
3
Clinical Significance
Conservation
PhyloP100: 6.50
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 |
---|---|---|---|---|---|---|---|---|
HP | NM_005143.5 | c.740T>C | p.Ile247Thr | missense_variant | 7/7 | ENST00000355906.10 | NP_005134.1 | |
HP | NM_001126102.3 | c.563T>C | p.Ile188Thr | missense_variant | 5/5 | NP_001119574.1 | ||
HP | NM_001318138.2 | c.563T>C | p.Ile188Thr | missense_variant | 5/5 | NP_001305067.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HP | ENST00000355906.10 | c.740T>C | p.Ile247Thr | missense_variant | 7/7 | 1 | NM_005143.5 | ENSP00000348170.5 | ||
TXNL4B | ENST00000562153.5 | c.285-16052A>G | intron_variant | 4 | ENSP00000454635.2 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152208Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
39
AN:
152208
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000802 AC: 20AN: 249424Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135324
GnomAD3 exomes
AF:
AC:
20
AN:
249424
Hom.:
AF XY:
AC XY:
14
AN XY:
135324
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727238
GnomAD4 exome
AF:
AC:
71
AN:
1461872
Hom.:
Cov.:
31
AF XY:
AC XY:
37
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000256 AC: 39AN: 152326Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74482
GnomAD4 genome
AF:
AC:
39
AN:
152326
Hom.:
Cov.:
31
AF XY:
AC XY:
16
AN XY:
74482
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
13
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Anhaptoglobinemia Other:1
Affects, no assertion criteria provided | literature only | OMIM | Apr 01, 2004 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Benign
DEOGEN2
Pathogenic
.;D;T;.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;M;.;.;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;D;D;.;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;D;D;.;.;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;.;.;.;.
Vest4
MVP
MPC
0.92
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at