rs1264216

Positions:

• chrX-66215415-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367233.3(HEPH):​c.2563+7169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 110,099 control chromosomes in the GnomAD database, including 4,247 homozygotes. There are 8,746 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 0.29 (4247 hom., 8746 hem., cov: 22)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPH	NM_001367233.3	c.2563+7169T>G		intron_variant		ENST00000343002.7	NP_001354162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPH	ENST00000343002.7	c.2563+7169T>G		intron_variant		1	NM_001367233.3	ENSP00000343939.2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31761 AN: 110049 Hom.: 4247 Cov.: 22 AF XY: 0.269 AC XY: 8707 AN XY: 32355

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00168

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.289 AC: 31796 AN: 110099 Hom.: 4247 Cov.: 22 AF XY: 0.270 AC XY: 8746 AN XY: 32415

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.00168

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.240

Alfa AF: 0.223 Hom.: 16242

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.81

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: rs1264216; hg19: chrX-65435257;