rs2070937

chr16-72055841-A-G

Variant summary

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

The NM_005143.5(HP):c.6-320A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 384,938 control chromosomes in the GnomAD database, including 60,709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (23944 hom., cov: 30)
  • Exomes 𝑓: 0.55 (36765 hom.)
• Consequence: HP NM_005143.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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: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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HP	NM_005143.5	c.6-320A>G		intron_variant		ENST00000355906.10
HP	NM_001126102.3	c.6-320A>G		intron_variant
HP	NM_001318138.2	c.6-320A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HP	ENST00000355906.10	c.6-320A>G		intron_variant		1	NM_005143.5	A2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84429 AN: 151608 Hom.: 23921 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.553 AC: 128913 AN: 233210 Hom.: 36765 Cov.: 3 AF XY: 0.563 AC XY: 71549 AN XY: 127148

Gnomad4 AFR exome AF: 0.624

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.705

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.557 AC: 84497 AN: 151728 Hom.: 23944 Cov.: 30 AF XY: 0.556 AC XY: 41215 AN XY: 74096

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.567

Alfa AF: 0.544 Hom.: 29473

Bravo AF: 0.544

Asia WGS AF: 0.514 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.053
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2070937; hg19: chr16-72089740; COSMIC: COSV63326413; COSMIC: COSV63326413;