Variant 11-94064373-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001098672.2(HEPHL1):c.671G>A(p.Arg224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,128 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 32 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 40 hom. )

Consequence

HEPHL1
NM_001098672.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.06

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001596272).

BP6

Variant 11-94064373-G-A is Benign according to our data. Variant chr11-94064373-G-A is described in ClinVar as [Benign]. Clinvar id is 3056170.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1793/152234) while in subpopulation AFR AF= 0.0397 (1649/41520). AF 95% confidence interval is 0.0381. There are 32 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPHL1	NM_001098672.2 linkuse as main transcript	c.671G>A	p.Arg224Gln	missense_variant	4/20	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.671G>A	p.Arg224Gln	missense_variant	4/20	5	NM_001098672.2	ENSP00000313699	P1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1791

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00675

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:

0.000206

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00300

AC:

747

AN:

248664

Hom.:

AF XY:

0.00232

AC XY:

313

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.0415

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00121

AC:

1769

AN:

1460894

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

792

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0118

AC:

1793

AN:

152234

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

831

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.00674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.0142

ESP6500AA

AF:

0.0384

AC:

144

ESP6500EA

AF:

0.000366

AC:

ExAC

AF:

0.00369

AC:

446

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEPHL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as 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

0.074

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.036

MetaRNN

Benign

0.0016

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

-0.57

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.16

REVEL

Benign

0.23

Sift

Benign

0.58

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.046

MVP

0.44

MPC

0.042

ClinPred

0.0025

GERP RS

0.14

Varity_R

0.037

gMVP

0.65

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