rs1028348

Variant names:

• chrX-66164321-C-A
• rs1028348
• NM_001367233.3:c.-163C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-66164321-C-A
• chrX-66164321-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367233.3(HEPH):​c.-163C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 640,451 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000016 (0 hom. 1 hem.)
• Consequence: HEPH NM_001367233.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 5 publications found

Genes affected

HEPH (HGNC:4866): (hephaestin) This gene encodes a member of the multicopper oxidase protein family. The encoded protein is involved in the transport of dietary iron from epithelial cells of the intestinal lumen into the circulatory system, and may be involved in copper transport and homeostasis. In mouse, defects in this gene can lead to severe microcytic anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

HEPH Gene-Disease associations (from GenCC):

• hereditary hemochromatosis

  Inheritance: XL Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367233.3. 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
	HEPH	NM_001367233.3	MANE Select	c.-163C>A		5_prime_UTR	Exon 1 of 21	NP_001354162.2	Q1HE23
	HEPH	NM_001367232.3		c.-188C>A		5_prime_UTR	Exon 1 of 21	NP_001354161.2	Q1HE23
	HEPH	NM_001130860.6		c.-163C>A		5_prime_UTR	Exon 1 of 21	NP_001124332.2	Q9BQS7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPH	ENST00000343002.7	TSL:1 MANE Select	c.-163C>A		5_prime_UTR	Exon 1 of 21	ENSP00000343939.2	Q9BQS7-1
	HEPH	ENST00000336279.9	TSL:1	c.-784C>A		5_prime_UTR	Exon 1 of 20	ENSP00000337418.5	Q9BQS7-4
	HEPH	ENST00000519389.6	TSL:1	c.-14+1445C>A		intron	N/A	ENSP00000430620.2	Q9BQS7-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000156 AC: 1 AN: 640451 Hom.: 0 Cov.: 22 AF XY: 0.00000521 AC XY: 1 AN XY: 192037

African (AFR) AF: 0.0000806 AC: 1 AN: 12402

American (AMR) AF: 0.00 AC: 0 AN: 817

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3971

East Asian (EAS) AF: 0.00 AC: 0 AN: 3025

South Asian (SAS) AF: 0.00 AC: 0 AN: 11995

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 265

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 585711

Other (OTH) AF: 0.00 AC: 0 AN: 21161

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 13000

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		0.22
PromoterAI		0.15	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1028348; hg19: chrX-65384163;