Variant 11-94063616-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001098672.2(HEPHL1):c.524C>T(p.Thr175Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000289 in 1,613,928 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

HEPHL1
NM_001098672.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.74

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01249665).

BP6

Variant 11-94063616-C-T is Benign according to our data. Variant chr11-94063616-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045219.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPHL1	NM_001098672.2 linkuse as main transcript	c.524C>T	p.Thr175Ile	missense_variant	3/20	ENST00000315765.10	NP_001092142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPHL1	ENST00000315765.10 linkuse as main transcript	c.524C>T	p.Thr175Ile	missense_variant	3/20	5	NM_001098672.2	ENSP00000313699	P1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000414

AC:

103

AN:

248912

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.00510

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

242

AN:

1461616

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00148

AC:

225

AN:

152312

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000310

Hom.:

Bravo

AF:

0.00171

ESP6500AA

AF:

0.00482

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000513

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEPHL1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.29

M_CAP

Benign

0.050

MetaRNN

Benign

0.012

MetaSVM

Uncertain

0.76

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.47

Sift

Benign

0.047

Sift4G

Uncertain

0.057

Polyphen

0.57

Vest4

0.44

MVP

0.68

MPC

0.18

ClinPred

0.078

GERP RS

4.5

Varity_R

0.24

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over