rs5471

Variant names:

• chr16-72054562-A-C
• rs5471
• NM_005143.5:c.-91A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-72054562-A-C
• chr16-72054562-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	NM_005143.5	MANE Select	c.-91A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_005134.1	P00738-1
	HP	NM_005143.5	MANE Select	c.-91A>C		5_prime_UTR	Exon 1 of 7	NP_005134.1	P00738-1
	HP	NM_001126102.3		c.-91A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001119574.1	P00738-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	ENST00000355906.10	TSL:1 MANE Select	c.-91A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000348170.5	P00738-1
	HP	ENST00000355906.10	TSL:1 MANE Select	c.-91A>C		5_prime_UTR	Exon 1 of 7	ENSP00000348170.5	P00738-1
	ENSG00000310525	ENST00000562153.6	TSL:4	n.285-10205T>G		intron	N/A	ENSP00000454635.2	H3BN11

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

GnomAD2 exomes AF: 0.00791 AC: 1636 AN: 206866 AF XY: 0.00584

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 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

African (AFR) AF: 0.128 AC: 4165 AN: 32652

American (AMR) AF: 0.00498 AC: 198 AN: 39746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 38204

South Asian (SAS) AF: 0.000277 AC: 23 AN: 83128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51724

Middle Eastern (MID) AF: 0.00349 AC: 20 AN: 5726

European-Non Finnish (NFE) AF: 0.0000785 AC: 86 AN: 1095600

Other (OTH) AF: 0.00746 AC: 442 AN: 59288

GnomAD4 genome AF: 0.0359 AC: 5471 AN: 152282 Hom.: 324 Cov.: 33 AF XY: 0.0343 AC XY: 2557 AN XY: 74462

African (AFR) AF: 0.126 AC: 5247 AN: 41556

American (AMR) AF: 0.0104 AC: 159 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68034

Other (OTH) AF: 0.0194 AC: 41 AN: 2108

Alfa AF: 0.0521 Hom.: 101

Bravo AF: 0.0404

ClinVar

ClinVar submissions

Significance: Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Anhaptoglobinemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		1.8
PromoterAI		-0.19	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5471; hg19: chr16-72088461;