rs7054364

chrX-66172794-C-AchrX-66172794-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HEPH	NM_001367233.3	c.412+195C>A		intron_variant		ENST00000343002.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000343002.7	c.412+195C>A		intron_variant		1	NM_001367233.3	P5

Frequencies

GnomAD3 genomes AF: 0.363 AC: 40229 AN: 110922 Hom.: 7828 Cov.: 23 AF XY: 0.346 AC XY: 11459 AN XY: 33156

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

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.00169

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.302

Alfa AF: 0.211 Hom.: 4291

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7054364; hg19: chrX-65392636;