rs1882694

Variant names:

• chr19-35280479-A-C
• rs1882694
• ENST00000827558.1:n.786T>G

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. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000827558.1(ENSG00000307628):​n.786T>G variant causes a non coding transcript exon 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: ENSG00000307628 ENST00000827558.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.84
• Publications: 15 publications found

Genes affected

ENSG00000307628 (HGNC:):

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]

HAMP Gene-Disease associations (from GenCC):

• hemochromatosis type 2B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hemochromatosis type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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
ENSG00000307628	ENST00000827558.1	n.786T>G		non_coding_transcript_exon_variant	Exon 2 of 2
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

African (AFR) AF: 0.630 AC: 26014 AN: 41280

American (AMR) AF: 0.408 AC: 6196 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1069 AN: 3456

East Asian (EAS) AF: 0.302 AC: 1541 AN: 5096

South Asian (SAS) AF: 0.414 AC: 1961 AN: 4736

European-Finnish (FIN) AF: 0.399 AC: 4153 AN: 10410

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24277 AN: 67628

Other (OTH) AF: 0.437 AC: 917 AN: 2100

Alfa AF: 0.385 Hom.: 32284

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
PhyloP100		-4.8
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1882694; hg19: chr19-35771382;