Variant 16-72076510-T-C 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.476T>C(p.Ile159Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000817 in 1,614,130 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 2 hom. )

Consequence

HPR
NM_020995.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

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=0.2293979).

BS2

High Homozygotes in GnomAdExome4 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.476T>C	p.Ile159Thr	missense_variant	5/5	ENST00000540303.7	NP_066275.3	P00739-1
HPR	NM_001384360.1 linkuse as main transcript	c.116T>C	p.Ile39Thr	missense_variant	6/6		NP_001371289.1
HPR	XM_024450251.2 linkuse as main transcript	c.494T>C	p.Ile165Thr	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.476T>C	p.Ile159Thr	missense_variant	5/5	1	NM_020995.4	ENSP00000441828.2		P00739-1
TXNL4B	ENST00000562153.5 linkuse as main transcript	c.284+12477A>G		intron_variant		4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000501

AC:

125

AN:

249272

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000929

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000844

AC:

1234

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000798

AC XY:

580

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000551

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000556

Hom.:

Bravo

AF:

0.000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000609

AC:

ExAC

AF:

0.000480

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000889

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

Jul 13, 2021

The c.476T>C (p.I159T) alteration is located in exon 5 (coding exon 5) of the HPR gene. This alteration results from a T to C substitution at nucleotide position 476, causing the isoleucine (I) at amino acid position 159 to be replaced by a threonine (T). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

0.077

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;.

REVEL

Uncertain

0.62

Sift

Benign

0.13

T;.

Sift4G

Uncertain

0.056

T;T

Polyphen

1.0

D;.

Vest4

0.54

MVP

0.82

MPC

0.54

ClinPred

0.092

GERP RS

2.5

Varity_R

0.27

gMVP

0.56

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