rs708969

chrX-66250053-A-T

Variant summary

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

The NM_001367233.3(HEPH):c.2564-4982A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 110,332 control chromosomes in the GnomAD database, including 3,963 homozygotes. There are 8,443 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 0.27 (3963 hom., 8443 hem., cov: 22)
• Consequence: HEPH NM_001367233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPH	NM_001367233.3	c.2564-4982A>T		intron_variant		ENST00000343002.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000343002.7	c.2564-4982A>T		intron_variant		1	NM_001367233.3	P5

Frequencies

GnomAD3 genomes AF: 0.274 AC: 30179 AN: 110280 Hom.: 3962 Cov.: 22 AF XY: 0.258 AC XY: 8406 AN XY: 32590

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.274 AC: 30215 AN: 110332 Hom.: 3963 Cov.: 22 AF XY: 0.259 AC XY: 8443 AN XY: 32652

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.00113

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.232

Alfa AF: 0.241 Hom.: 1675

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.38
Dann	Benign	0.62

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: rs708969; hg19: chrX-65469895;