Genetic Variant NM_005143.5:c.214A>C (chr16-72057415-A-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005143.5(HP):c.214A>C(p.Lys72Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K72E) has been classified as Benign.

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

HP
NM_005143.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2714107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HP	NM_005143.5 link	c.214A>C	p.Lys72Gln	missense_variant	Exon 4 of 7	ENST00000355906.10	NP_005134.1	P00738-1Q6PEJ8
HP	NM_001318138.2 link	c.214A>C	p.Lys72Gln	missense_variant	Exon 4 of 5		NP_001305067.1	P00738Q6PEJ8A0A0C4DGL8
HP	NM_001126102.3 link	c.190+784A>C		intron_variant	Intron 3 of 4		NP_001119574.1	P00738-2Q6PEJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HP	ENST00000355906.10 link	c.214A>C	p.Lys72Gln	missense_variant	Exon 4 of 7	1	NM_005143.5	ENSP00000348170.5		P00738-1
ENSG00000310525	ENST00000562153.6 link	n.285-13058T>G		intron_variant	Intron 3 of 5	4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000105

AC:

AN:

949058

Hom.:

Cov.:

AF XY:

0.00000207

AC XY:

AN XY:

482782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23260

American (AMR)

AF:

0.00

AC:

AN:

27952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21716

East Asian (EAS)

AF:

0.0000318

AC:

AN:

31440

South Asian (SAS)

AF:

0.00

AC:

AN:

73114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

677394

Other (OTH)

AF:

0.00

AC:

AN:

42928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.31

T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.079

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.064

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.0

M;.;.

PhyloP100

2.4

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.31

N;.;N

REVEL

Benign

0.16

Sift

Benign

0.40

T;.;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.31

MutPred

0.49

Loss of ubiquitination at K72 (P = 0.0244);Loss of ubiquitination at K72 (P = 0.0244);Loss of ubiquitination at K72 (P = 0.0244);

MVP

0.57

MPC

0.48

ClinPred

0.42

GERP RS

3.2

Varity_R

0.12

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over