Variant 16-72054562-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005143.5(HP):c.-91A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,583,926 control chromosomes in the GnomAD database, including 610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.036 ( 324 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 286 hom. )

Consequence

HP
NM_005143.5 5_prime_UTR

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 1.84

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
HP	NM_005143.5 linkuse as main transcript	c.-91A>C	5_prime_UTR_variant	1/7	ENST00000355906.10
HP	NM_001126102.3 linkuse as main transcript	c.-91A>C	5_prime_UTR_variant	1/5
HP	NM_001318138.2 linkuse as main transcript	c.-91A>C	5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HP	ENST00000355906.10 linkuse as main transcript	c.-91A>C	5_prime_UTR_variant	1/7	1	NM_005143.5	A2	P00738-1
TXNL4B	ENST00000562153.5 linkuse as main transcript	c.285-10205T>G	intron_variant		4
HP	ENST00000398131.6 linkuse as main transcript		upstream_gene_variant		1		P3	P00738-2
HP	ENST00000570083.5 linkuse as main transcript		upstream_gene_variant		1		P3	P00738-2

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5468

AN:

152164

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.00791

AC:

1636

AN:

206866

Hom.:

AF XY:

0.00584

AC XY:

652

AN XY:

111630

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.00413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000221

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00345

AC:

4934

AN:

1431644

Hom.:

286

Cov.:

AF XY:

0.00298

AC XY:

2112

AN XY:

709696

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.00498

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000277

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000785

Gnomad4 OTH exome

AF:

0.00746

GnomAD4 genome

AF:

0.0359

AC:

5471

AN:

152282

Hom.:

324

Cov.:

AF XY:

0.0343

AC XY:

2557

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0210

Hom.:

Bravo

AF:

0.0404

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Anhaptoglobinemia

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Nov 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

Dann

Benign

0.58

Splicing

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