Variant chr16-72076505-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020995.4(HPR):c.471A>T(p.Lys157Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,166 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

HPR
NM_020995.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.452

Variant links:

Genes affected

HPR (HGNC:5156): (haptoglobin-related protein) This gene encodes a haptoglobin-related protein that binds hemoglobin as efficiently as haptoglobin. Unlike haptoglobin, plasma concentration of this protein is unaffected in patients with sickle cell anemia and extensive intravascular hemolysis, suggesting a difference in binding between haptoglobin-hemoglobin and haptoglobin-related protein-hemoglobin complexes to CD163, the hemoglobin scavenger receptor. This protein may also be a clinically important predictor of recurrence of breast cancer. [provided by RefSeq, Oct 2011]

HPR links:

TXNL4B (HGNC:):

TXNL4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08948457).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPR	NM_020995.4 linkuse as main transcript	c.471A>T	p.Lys157Asn	missense_variant	5/5	ENST00000540303.7	NP_066275.3	P00739-1
HPR	NM_001384360.1 linkuse as main transcript	c.111A>T	p.Lys37Asn	missense_variant	6/6		NP_001371289.1
HPR	XM_024450251.2 linkuse as main transcript	c.489A>T	p.Lys163Asn	missense_variant	5/5		XP_024306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPR	ENST00000540303.7 linkuse as main transcript	c.471A>T	p.Lys157Asn	missense_variant	5/5	1	NM_020995.4	ENSP00000441828.2		P00739-1
TXNL4B	ENST00000562153.5 linkuse as main transcript	c.284+12482T>A		intron_variant		4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249300

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000992

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000217

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.471A>T (p.K157N) alteration is located in exon 5 (coding exon 5) of the HPR gene. This alteration results from a A to T substitution at nucleotide position 471, causing the lysine (K) at amino acid position 157 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.97

N;.

REVEL

Benign

0.24

Sift

Benign

0.35

T;.

Sift4G

Benign

0.38

T;T

Polyphen

0.0060

B;.

Vest4

0.12

MutPred

0.56

Loss of ubiquitination at K157 (P = 0.0192);.;

MVP

0.52

MPC

0.13

ClinPred

0.013

GERP RS

-4.9

Varity_R

0.12

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over