rs1882694

Variant names:

• chr19-35280479-A-C
• rs1882694
• ENST00000598398.5:c.-533A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-35280479-A-C
• chr19-35280479-A-G
• chr19-35280479-A-T

Variant summary

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

The ENST00000598398.5(HAMP):​c.-533A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,092 control chromosomes in the GnomAD database, including 15,616 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 0.44 (15616 hom., cov: 32)
• Consequence: HAMP ENST00000598398.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.84

Genes affected

HAMP (HGNC:15598): (hepcidin antimicrobial peptide) The product encoded by this gene is involved in the maintenance of iron homeostasis, and it is necessary for the regulation of iron storage in macrophages, and for intestinal iron absorption. The preproprotein is post-translationally cleaved into mature peptides of 20, 22 and 25 amino acids, and these active peptides are rich in cysteines, which form intramolecular bonds that stabilize their beta-sheet structures. These peptides exhibit antimicrobial activity against bacteria and fungi. Mutations in this gene cause hemochromatosis type 2B, also known as juvenile hemochromatosis, a disease caused by severe iron overload that results in cardiomyopathy, cirrhosis, and endocrine failure. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAMP	ENST00000598398.5	c.-533A>C		upstream_gene_variant		2		ENSP00000471894.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66453 AN: 150976 Hom.: 15608 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66509 AN: 151092 Hom.: 15616 Cov.: 32 AF XY: 0.441 AC XY: 32555 AN XY: 73744

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.437

Alfa AF: 0.363 Hom.: 16160

Bravo AF: 0.445

Asia WGS AF: 0.372 AC: 1296 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1882694; hg19: chr19-35771382;