rs2460063

Variant names:

• chr11-94063062-T-C
• rs2460063
• NM_001098672.2:c.416-446T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

HEPHL1 Gene-Disease associations (from GenCC):

• pili torti-developmental delay-neurological abnormalities syndrome

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPHL1	NM_001098672.2	MANE Select	c.416-446T>C		intron	N/A	NP_001092142.1	Q6MZM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPHL1	ENST00000315765.10	TSL:5 MANE Select	c.416-446T>C		intron	N/A	ENSP00000313699.9	Q6MZM0

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

African (AFR) AF: 0.207 AC: 8478 AN: 41048

American (AMR) AF: 0.453 AC: 6857 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1357 AN: 3450

East Asian (EAS) AF: 0.376 AC: 1911 AN: 5078

South Asian (SAS) AF: 0.318 AC: 1517 AN: 4768

European-Finnish (FIN) AF: 0.422 AC: 4456 AN: 10556

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27697 AN: 67518

Other (OTH) AF: 0.388 AC: 807 AN: 2082

Alfa AF: 0.366 Hom.: 1380

Bravo AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.9
DANN	Benign	0.86
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2460063; hg19: chr11-93796228;