chr11-94051138-G-A

Variant names:

• chr11-94051138-G-A
• rs7946162
• NM_001098672.2:c.415+5221G>A

Variant summary

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

The NM_001098672.2(HEPHL1):​c.415+5221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,864 control chromosomes in the GnomAD database, including 25,908 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 0.58 (25908 hom., cov: 32)
• Consequence: HEPHL1 NM_001098672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPHL1	NM_001098672.2	c.415+5221G>A		intron_variant	Intron 2 of 19	ENST00000315765.10	NP_001092142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPHL1	ENST00000315765.10	c.415+5221G>A		intron_variant	Intron 2 of 19	5	NM_001098672.2	ENSP00000313699.9

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88349 AN: 151746 Hom.: 25896 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.582 AC: 88419 AN: 151864 Hom.: 25908 Cov.: 32 AF XY: 0.585 AC XY: 43456 AN XY: 74234

African (AFR) AF: 0.577 AC: 23883 AN: 41374

American (AMR) AF: 0.524 AC: 8008 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2089 AN: 3462

East Asian (EAS) AF: 0.623 AC: 3226 AN: 5180

South Asian (SAS) AF: 0.680 AC: 3273 AN: 4814

European-Finnish (FIN) AF: 0.579 AC: 6112 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39810 AN: 67886

Other (OTH) AF: 0.569 AC: 1201 AN: 2112

Alfa AF: 0.576 Hom.: 3277

Bravo AF: 0.573

Asia WGS AF: 0.624 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.96
DANN	Benign	0.60
PhyloP100		-0.71
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: rs7946162; hg19: chr11-93784304;