chr16-72054568-A-G

Variant names:

• chr16-72054568-A-G
• rs5472
• NM_005143.5:c.-85A>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.-85A>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 0.328 in 146,828 control chromosomes in the GnomAD database, including 4,530 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 0.33 (4530 hom., cov: 32)
  • Exomes 𝑓: 0.30 (6406 hom.)
  • Failed GnomAD Quality Control
• Consequence: HP NM_005143.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 21 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 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.-85A>G		5_prime_UTR	Exon 1 of 7	NP_005134.1	P00738-1
	HP	NM_001126102.3		c.-85A>G		5_prime_UTR	Exon 1 of 5	NP_001119574.1	P00738-2
	HP	NM_001318138.2		c.-85A>G		5_prime_UTR	Exon 1 of 5	NP_001305067.1	A0A0C4DGL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	ENST00000355906.10	TSL:1 MANE Select	c.-85A>G		5_prime_UTR	Exon 1 of 7	ENSP00000348170.5	P00738-1
	ENSG00000310525	ENST00000562153.6	TSL:4	n.285-10211T>C		intron	N/A	ENSP00000454635.2	H3BN11
	HP	ENST00000398131.6	TSL:1	c.-85A>G		upstream_gene	N/A	ENSP00000381199.2	P00738-2

Frequencies

GnomAD3 genomes AF: 0.328 AC: 48192 AN: 146714 Hom.: 4528 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.307 AC: 63264 AN: 205912 AF XY: 0.314

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.318

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.299 AC: 424216 AN: 1420780 Hom.: 6406 Cov.: 35 AF XY: 0.301 AC XY: 212131 AN XY: 704288

African (AFR) AF: 0.346 AC: 11157 AN: 32210

American (AMR) AF: 0.240 AC: 9534 AN: 39708

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8604 AN: 25240

East Asian (EAS) AF: 0.280 AC: 10526 AN: 37640

South Asian (SAS) AF: 0.359 AC: 29556 AN: 82388

European-Finnish (FIN) AF: 0.299 AC: 15371 AN: 51358

Middle Eastern (MID) AF: 0.353 AC: 1994 AN: 5644

European-Non Finnish (NFE) AF: 0.294 AC: 319417 AN: 1087962

Other (OTH) AF: 0.308 AC: 18057 AN: 58630

GnomAD4 genome AF: 0.328 AC: 48217 AN: 146828 Hom.: 4530 Cov.: 32 AF XY: 0.326 AC XY: 23410 AN XY: 71838

African (AFR) AF: 0.369 AC: 14601 AN: 39516

American (AMR) AF: 0.278 AC: 4153 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1169 AN: 3324

East Asian (EAS) AF: 0.261 AC: 1317 AN: 5040

South Asian (SAS) AF: 0.400 AC: 1830 AN: 4580

European-Finnish (FIN) AF: 0.309 AC: 3164 AN: 10254

Middle Eastern (MID) AF: 0.451 AC: 130 AN: 288

European-Non Finnish (NFE) AF: 0.318 AC: 20966 AN: 65992

Other (OTH) AF: 0.335 AC: 677 AN: 2018

Alfa AF: 0.332 Hom.: 819

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		-0.25
PromoterAI		0.056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5472; hg19: chr16-72088467; COSMIC: COSV63325898;