rs1264216

Variant names:

• chrX-66215415-T-A
• rs1264216
• NM_001367233.3:c.2563+7169T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-66215415-T-A
• chrX-66215415-T-G

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.2563+7169T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000908 in 110,167 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: 𝑓 0.0000091 (0 hom., 1 hem., cov: 22)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760
• Publications: 0 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=-0.85).

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.2563+7169T>A		intron	N/A	NP_001354162.2	Q1HE23
	HEPH	NM_001367232.3		c.2563+7169T>A		intron	N/A	NP_001354161.2	Q1HE23
	HEPH	NM_001367234.3		c.2563+7169T>A		intron	N/A	NP_001354163.2	Q1HE23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPH	ENST00000343002.7	TSL:1 MANE Select	c.2563+7169T>A		intron	N/A	ENSP00000343939.2	Q9BQS7-1
	HEPH	ENST00000519389.6	TSL:1	c.2563+7169T>A		intron	N/A	ENSP00000430620.2	Q9BQS7-1
	HEPH	ENST00000441993.7	TSL:1	c.2563+7169T>A		intron	N/A	ENSP00000411687.3	Q9BQS7-2

Frequencies

GnomAD3 genomes AF: 0.00000908 AC: 1 AN: 110117 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000908 AC: 1 AN: 110167 Hom.: 0 Cov.: 22 AF XY: 0.0000308 AC XY: 1 AN XY: 32449

African (AFR) AF: 0.00 AC: 0 AN: 30096

American (AMR) AF: 0.00 AC: 0 AN: 10335

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00 AC: 0 AN: 2597

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5721

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52817

Other (OTH) AF: 0.00 AC: 0 AN: 1504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1264216; hg19: chrX-65435257;