rs1011526

Positions:

• chrX-66196245-G-A

Variant summary

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

The NM_001367233.3(HEPH):​c.1501+1016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 110,338 control chromosomes in the GnomAD database, including 9,518 homozygotes. There are 12,116 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 0.39 (9518 hom., 12116 hem., cov: 22)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPH	NM_001367233.3	c.1501+1016G>A		intron_variant		ENST00000343002.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000343002.7	c.1501+1016G>A		intron_variant		1	NM_001367233.3	P5

Frequencies

GnomAD3 genomes AF: 0.390 AC: 42967 AN: 110286 Hom.: 9508 Cov.: 22 AF XY: 0.371 AC XY: 12063 AN XY: 32540

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.390 AC: 43032 AN: 110338 Hom.: 9518 Cov.: 22 AF XY: 0.372 AC XY: 12116 AN XY: 32602

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00141

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.323

Alfa AF: 0.246 Hom.: 12880

Bravo AF: 0.411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.84

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: rs1011526; hg19: chrX-65416087;