rs1518563

Variant names:

• chr11-94032154-T-C
• rs1518563
• NM_001098672.2:c.170+10616T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098672.2(HEPHL1):​c.170+10616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,156 control chromosomes in the GnomAD database, including 9,318 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 0.32 (9318 hom., cov: 32)
• Consequence: HEPHL1 NM_001098672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• 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 Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPHL1	NM_001098672.2	c.170+10616T>C		intron_variant	Intron 1 of 19	ENST00000315765.10	NP_001092142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPHL1	ENST00000315765.10	c.170+10616T>C		intron_variant	Intron 1 of 19	5	NM_001098672.2	ENSP00000313699.9

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49406 AN: 152038 Hom.: 9326 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.325 AC: 49396 AN: 152156 Hom.: 9318 Cov.: 32 AF XY: 0.327 AC XY: 24338 AN XY: 74368

African (AFR) AF: 0.118 AC: 4893 AN: 41542

American (AMR) AF: 0.376 AC: 5741 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3464

East Asian (EAS) AF: 0.308 AC: 1593 AN: 5170

South Asian (SAS) AF: 0.444 AC: 2137 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3911 AN: 10570

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28350 AN: 67986

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.354 Hom.: 3794

Bravo AF: 0.309

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.90
PhyloP100		0.40
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: rs1518563; hg19: chr11-93765320;