rs5470

Variant names:

• chr16-72054522-C-G
• rs5470
• NM_005143.5:c.-131C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-72054522-C-G
• chr16-72054522-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005143.5(HP):​c.-131C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,560,710 control chromosomes in the GnomAD database, including 612 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 0.038 (318 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (294 hom.)
• Consequence: HP NM_005143.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757
• Publications: 9 publications found

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]

ENSG00000310525 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005143.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	NM_005143.5	MANE Select	c.-131C>G		5_prime_UTR	Exon 1 of 7	NP_005134.1
	HP	NM_001126102.3		c.-131C>G		5_prime_UTR	Exon 1 of 5	NP_001119574.1
	HP	NM_001318138.2		c.-131C>G		5_prime_UTR	Exon 1 of 5	NP_001305067.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	ENST00000355906.10	TSL:1 MANE Select	c.-131C>G		5_prime_UTR	Exon 1 of 7	ENSP00000348170.5
	ENSG00000310525	ENST00000562153.6	TSL:4	n.285-10165G>C		intron	N/A	ENSP00000454635.2
	HP	ENST00000398131.6	TSL:1	c.-131C>G		upstream_gene	N/A	ENSP00000381199.2

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5731 AN: 152046 Hom.: 317 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.00376 AC: 5302 AN: 1408546 Hom.: 294 AF XY: 0.00320 AC XY: 2229 AN XY: 696426

African (AFR) AF: 0.131 AC: 4174 AN: 31866

American (AMR) AF: 0.00764 AC: 284 AN: 37152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25308

East Asian (EAS) AF: 0.00 AC: 0 AN: 36868

South Asian (SAS) AF: 0.000173 AC: 14 AN: 80832

European-Finnish (FIN) AF: 0.0000594 AC: 3 AN: 50470

Middle Eastern (MID) AF: 0.00439 AC: 25 AN: 5698

European-Non Finnish (NFE) AF: 0.000290 AC: 314 AN: 1081924

Other (OTH) AF: 0.00835 AC: 488 AN: 58428

GnomAD4 genome AF: 0.0377 AC: 5744 AN: 152164 Hom.: 318 Cov.: 33 AF XY: 0.0369 AC XY: 2743 AN XY: 74378

African (AFR) AF: 0.131 AC: 5433 AN: 41480

American (AMR) AF: 0.0139 AC: 213 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68022

Other (OTH) AF: 0.0274 AC: 58 AN: 2116

Alfa AF: 0.000883 Hom.: 2

Bravo AF: 0.0428

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.76
PromoterAI		-0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5470; hg19: chr16-72088421;