NM_005143.5:c.112G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005143.5(HP):c.112G>A(p.Glu38Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,488,700 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 21)

Exomes 𝑓: 0.0044 ( 15 hom. )

Consequence

HP
NM_005143.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0730

Publications

2 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006028712).

BP6

Variant 16-72056553-G-A is Benign according to our data. Variant chr16-72056553-G-A is described in ClinVar as Benign. ClinVar VariationId is 777878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

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.112G>A	p.Glu38Lys	missense	Exon 3 of 7	NP_005134.1	P00738-1
HP	NM_001126102.3		c.112G>A	p.Glu38Lys	missense	Exon 3 of 5	NP_001119574.1	P00738-2
HP	NM_001318138.2		c.112G>A	p.Glu38Lys	missense	Exon 3 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.112G>A	p.Glu38Lys	missense	Exon 3 of 7	ENSP00000348170.5	P00738-1
HP	ENST00000398131.6	TSL:1	c.112G>A	p.Glu38Lys	missense	Exon 3 of 5	ENSP00000381199.2	P00738-2
HP	ENST00000565574.5	TSL:1	c.112G>A	p.Glu38Lys	missense	Exon 3 of 5	ENSP00000454966.1	A0A0C4DGL8

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

394

AN:

135384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00611

Gnomad ASJ

AF:

0.000302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00290

GnomAD2 exomes

AF:

0.00296

AC:

475

AN:

160454

AF XY:

0.00297

show subpopulations

Gnomad AFR exome

AF:

0.000764

Gnomad AMR exome

AF:

0.00505

Gnomad ASJ exome

AF:

0.000826

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000352

Gnomad NFE exome

AF:

0.00496

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00439

AC:

5945

AN:

1353208

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

2849

AN XY:

669948

show subpopulations

African (AFR)

AF:

0.000586

AC:

AN:

30696

American (AMR)

AF:

0.00493

AC:

176

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.000563

AC:

AN:

24860

East Asian (EAS)

AF:

0.00

AC:

AN:

35572

South Asian (SAS)

AF:

0.000115

AC:

AN:

78414

European-Finnish (FIN)

AF:

0.000404

AC:

AN:

49496

Middle Eastern (MID)

AF:

0.00117

AC:

AN:

4288

European-Non Finnish (NFE)

AF:

0.00529

AC:

5490

AN:

1037834

Other (OTH)

AF:

0.00378

AC:

213

AN:

56360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

284

567

851

1134

1418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<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:

0.00291

AC:

394

AN:

135492

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

171

AN XY:

65020

show subpopulations

African (AFR)

AF:

0.000937

AC:

AN:

35210

American (AMR)

AF:

0.00611

AC:

AN:

13102

Ashkenazi Jewish (ASJ)

AF:

0.000302

AC:

AN:

3310

East Asian (EAS)

AF:

0.00

AC:

AN:

4458

South Asian (SAS)

AF:

0.00

AC:

AN:

3656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00431

AC:

275

AN:

63834

Other (OTH)

AF:

0.00287

AC:

AN:

1744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

102

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:

0.00315

Hom.:

Bravo

AF:

0.00344

ESP6500AA

AF:

0.000875

AC:

ESP6500EA

AF:

0.00450

AC:

ExAC

AF:

0.00168

AC:

189

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.6

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.30

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.023

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

-0.073

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.34

REVEL

Benign

0.14

Sift

Benign

0.10

Sift4G

Benign

0.15

Polyphen

0.17

Vest4

0.22

MVP

0.19

MPC

0.28

ClinPred

0.0062

GERP RS

-2.3

PromoterAI

0.015

Neutral

(source)

Varity_R

0.029

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over