Variant 16-72060233-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005143.5(HP):c.564T>G(p.Gly188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 152,266 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 23 hom. )

Failed GnomAD Quality Control

Consequence

HP
NM_005143.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.911

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 16-72060233-T-G is Benign according to our data. Variant chr16-72060233-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 782963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.911 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HP	NM_005143.5 linkuse as main transcript	c.564T>G	p.Gly188=	synonymous_variant	7/7	ENST00000355906.10
HP	NM_001126102.3 linkuse as main transcript	c.387T>G	p.Gly129=	synonymous_variant	5/5
HP	NM_001318138.2 linkuse as main transcript	c.387T>G	p.Gly129=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HP	ENST00000355906.10 linkuse as main transcript	c.564T>G	p.Gly188=	synonymous_variant	7/7	1	NM_005143.5	A2	P00738-1

Frequencies

GnomAD3 genomes

AF:

0.00327

AC:

497

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00285

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00144

AC:

359

AN:

248890

Hom.:

AF XY:

0.00143

AC XY:

193

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.00285

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00184

Gnomad SAS exome

AF:

0.00161

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00156

AC:

2269

AN:

1458452

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1152

AN XY:

725608

show subpopulations

Gnomad4 AFR exome

AF:

0.00282

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00232

Gnomad4 SAS exome

AF:

0.00253

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00327

AC:

498

AN:

152266

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00501

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00285

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00329

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	HP: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.3

DANN

Benign

0.58

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