chr16-72056553-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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:

TXNL4B (HGNC:26041): (thioredoxin like 4B) Predicted to be involved in mRNA splicing, via spliceosome. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TXNL4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 777878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HP	NM_005143.5 link	c.112G>A	p.Glu38Lys	missense_variant	Exon 3 of 7	ENST00000355906.10	NP_005134.1	P00738-1Q6PEJ8
HP	NM_001126102.3 link	c.112G>A	p.Glu38Lys	missense_variant	Exon 3 of 5		NP_001119574.1	P00738-2Q6PEJ8
HP	NM_001318138.2 link	c.112G>A	p.Glu38Lys	missense_variant	Exon 3 of 5		NP_001305067.1	P00738Q6PEJ8A0A0C4DGL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HP	ENST00000355906.10 link	c.112G>A	p.Glu38Lys	missense_variant	Exon 3 of 7	1	NM_005143.5	ENSP00000348170.5		P00738-1
TXNL4B	ENST00000562153.5 link	c.285-12196C>T		intron_variant	Intron 3 of 3	4		ENSP00000454635.2		H3BN11

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

GnomAD3 exomes

AF:

0.00296

AC:

475

AN:

160454

Hom.:

AF XY:

0.00297

AC XY:

253

AN XY:

85232

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 SAS exome

AF:

0.000129

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

Gnomad4 AFR exome

AF:

0.000586

Gnomad4 AMR exome

AF:

0.00493

Gnomad4 ASJ exome

AF:

0.000563

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.000404

Gnomad4 NFE exome

AF:

0.00529

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00291

AC:

394

AN:

135492

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

171

AN XY:

65020

show subpopulations

Gnomad4 AFR

AF:

0.000937

Gnomad4 AMR

AF:

0.00611

Gnomad4 ASJ

AF:

0.000302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00287

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00344

ESP6500AA

AF:

0.000875

AC:

ESP6500EA

AF:

0.00450

AC:

ExAC

AF:

0.00168

AC:

189

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.6

DANN

Benign

0.70

DEOGEN2

Benign

0.30

T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.023

LIST_S2

Uncertain

0.88

D;T;T;T

MetaRNN

Benign

0.0060

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.34

N;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.10

T;T;.;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.17

B;.;.;.

Vest4

0.22

MVP

0.19

MPC

0.28

ClinPred

0.0062

GERP RS

-2.3

Varity_R

0.029

gMVP

0.35

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