X-66243655-A-G

Position:

• chrX-66243655-A-G

Variant summary

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

The NM_001367233.3(HEPH):​c.2564-11380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 112,121 control chromosomes in the GnomAD database, including 9,385 homozygotes. There are 12,552 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 0.38 (9385 hom., 12552 hem., cov: 25)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPH	NM_001367233.3	c.2564-11380A>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.2564-11380A>G		intron_variant		1	NM_001367233.3	ENSP00000343939.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 42386 AN: 112068 Hom.: 9376 Cov.: 25 AF XY: 0.364 AC XY: 12497 AN XY: 34288

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.379 AC: 42451 AN: 112121 Hom.: 9385 Cov.: 25 AF XY: 0.365 AC XY: 12552 AN XY: 34351

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.00112

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.309

Alfa AF: 0.196 Hom.: 3262

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.49

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: rs1068536; hg19: chrX-65463497;