rs7054364

Variant names:

• chrX-66172794-C-A
• rs7054364
• NM_001367233.3:c.412+195C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-66172794-C-A
• chrX-66172794-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367233.3(HEPH):​c.412+195C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 110,976 control chromosomes in the GnomAD database, including 7,836 homozygotes. There are 11,507 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 0.36 (7836 hom., 11507 hem., cov: 23)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPH	NM_001367233.3	c.412+195C>A		intron_variant	Intron 3 of 20	ENST00000343002.7	NP_001354162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPH	ENST00000343002.7	c.412+195C>A		intron_variant	Intron 3 of 20	1	NM_001367233.3	ENSP00000343939.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 40229 AN: 110922 Hom.: 7828 Cov.: 23

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.363 AC: 40286 AN: 110976 Hom.: 7836 Cov.: 23 AF XY: 0.346 AC XY: 11507 AN XY: 33220

African (AFR) AF: 0.763 AC: 23237 AN: 30449

American (AMR) AF: 0.247 AC: 2583 AN: 10478

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 541 AN: 2627

East Asian (EAS) AF: 0.00169 AC: 6 AN: 3540

South Asian (SAS) AF: 0.106 AC: 284 AN: 2676

European-Finnish (FIN) AF: 0.258 AC: 1523 AN: 5913

Middle Eastern (MID) AF: 0.222 AC: 48 AN: 216

European-Non Finnish (NFE) AF: 0.218 AC: 11505 AN: 52884

Other (OTH) AF: 0.302 AC: 458 AN: 1518

Alfa AF: 0.212 Hom.: 4820

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7054364; hg19: chrX-65392636;