Variant chr11-94045743-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001098672.2(HEPHL1):c.241C>T(p.Arg81Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,613,644 control chromosomes in the GnomAD database, including 4 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 0.0018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

HEPHL1
NM_001098672.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.02

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012653142).

BP6

Variant 11-94045743-C-T is Benign according to our data. Variant chr11-94045743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033145.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPHL1	NM_001098672.2 linkuse as main transcript	c.241C>T	p.Arg81Cys	missense_variant	2/20	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.241C>T	p.Arg81Cys	missense_variant	2/20	5	NM_001098672.2	ENSP00000313699	P1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00606

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000539

AC:

134

AN:

248614

Hom.:

AF XY:

0.000452

AC XY:

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.00667

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000332

AC:

485

AN:

1461370

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00693

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152274

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00602

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.00206

ESP6500AA

AF:

0.00462

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000588

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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 16, 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

0.084

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.013

MetaSVM

Pathogenic

0.86

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.99

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.50

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.59

Vest4

0.31

MVP

0.68

MPC

0.13

ClinPred

0.088

GERP RS

5.2

Varity_R

0.28

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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