16-72054562-A-C

Position:

• chr16-72054562-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005143.5(HP):​c.-91A>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 1.84

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]

TXNL4B (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HP	NM_005143.5	c.-91A>C		5_prime_UTR_premature_start_codon_gain_variant	1/7	ENST00000355906.10	NP_005134.1
HP	NM_005143.5	c.-91A>C		5_prime_UTR_variant	1/7	ENST00000355906.10	NP_005134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HP	ENST00000355906	c.-91A>C		5_prime_UTR_premature_start_codon_gain_variant	1/7	1	NM_005143.5	ENSP00000348170.5
HP	ENST00000355906	c.-91A>C		5_prime_UTR_variant	1/7	1	NM_005143.5	ENSP00000348170.5
TXNL4B	ENST00000562153.5	c.285-10205T>G		intron_variant		4		ENSP00000454635.2

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5468 AN: 152164 Hom.: 324 Cov.: 33

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.: 95 AF XY: 0.00584 AC XY: 652 AN XY: 111630

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.: 32 AF XY: 0.00298 AC XY: 2112 AN XY: 709696

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.: 33 AF XY: 0.0343 AC XY: 2557 AN XY: 74462

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.: 31

Bravo AF: 0.0404

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

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	12
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5471; hg19: chr16-72088461;