rs2460063

Positions:

• chr11-94063062-T-C
• chr11-94063062-T-G

Variant summary

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

The NM_001098672.2(HEPHL1):​c.416-446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 150,844 control chromosomes in the GnomAD database, including 10,004 homozygotes. 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 0.35 (10004 hom., cov: 31)
• Consequence: HEPHL1 NM_001098672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

HEPHL1 (HGNC:30477): (hephaestin like 1) Enables ferroxidase activity. Involved in cellular iron ion homeostasis. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPHL1	NM_001098672.2	c.416-446T>C		intron_variant		ENST00000315765.10	NP_001092142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPHL1	ENST00000315765.10	c.416-446T>C		intron_variant		5	NM_001098672.2	ENSP00000313699	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53429 AN: 150726 Hom.: 10003 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.354 AC: 53455 AN: 150844 Hom.: 10004 Cov.: 31 AF XY: 0.354 AC XY: 26125 AN XY: 73760

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.388

Alfa AF: 0.372 Hom.: 1361

Bravo AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.9
DANN	Benign	0.86

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: rs2460063; hg19: chr11-93796228;