chr16-72058266-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_005143.5(HP):c.278C>T(p.Pro93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000036 ( 3 hom. )

Consequence

HP
NM_005143.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33305523).

BP6

Variant 16-72058266-C-T is Benign according to our data. Variant chr16-72058266-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3526449.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 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.278C>T	p.Pro93Leu	missense	Exon 5 of 7	NP_005134.1	P00738-1
HP	NM_001126102.3		c.191-848C>T		intron	N/A	NP_001119574.1	P00738-2
HP	NM_001318138.2		c.265+800C>T		intron	N/A	NP_001305067.1	A0A0C4DGL8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HP	ENST00000355906.10	TSL:1 MANE Select	c.278C>T	p.Pro93Leu	missense	Exon 5 of 7	ENSP00000348170.5	P00738-1
HP	ENST00000570083.5	TSL:1	c.101C>T	p.Pro34Leu	missense	Exon 3 of 5	ENSP00000457629.1	P00738-2
HP	ENST00000398131.6	TSL:1	c.191-848C>T		intron	N/A	ENSP00000381199.2	P00738-2

Frequencies

GnomAD3 genomes

AF:

0.0000392

AC:

AN:

76496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000256

Gnomad OTH

AF:

0.00102

GnomAD2 exomes

AF:

0.0000352

AC:

AN:

113676

AF XY:

0.0000486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

880548

Hom.:

Cov.:

AF XY:

0.0000379

AC XY:

AN XY:

448166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15748

American (AMR)

AF:

0.0000412

AC:

AN:

24246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19632

East Asian (EAS)

AF:

0.00

AC:

AN:

30600

South Asian (SAS)

AF:

0.0000423

AC:

AN:

70844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3232

European-Non Finnish (NFE)

AF:

0.0000440

AC:

AN:

636816

Other (OTH)

AF:

0.00

AC:

AN:

38836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000392

AC:

AN:

76496

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

36756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14948

American (AMR)

AF:

0.00

AC:

AN:

6714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2248

East Asian (EAS)

AF:

0.00

AC:

AN:

3254

South Asian (SAS)

AF:

0.00

AC:

AN:

3034

European-Finnish (FIN)

AF:

0.000182

AC:

AN:

5494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0000256

AC:

AN:

39082

Other (OTH)

AF:

0.00102

AC:

AN:

984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000130

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.050

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

PhyloP100

1.2

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.24

Sift

Benign

0.10

Sift4G

Uncertain

0.0060

Polyphen

0.057

Vest4

0.15

MutPred

0.51

Loss of disorder (P = 0.0182)

MVP

0.71

MPC

0.26

ClinPred

0.082

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.46

Mutation Taster

=90/10

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over