Variant 1-152218606-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001009931.3(HRNR):c.3023G>C(p.Ser1008Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,610,884 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 16 hom. )

Consequence

HRNR
NM_001009931.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

HRNR (HGNC:20846): (hornerin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Involved in cell envelope organization and establishment of skin barrier. Located in cornified envelope; keratohyalin granule; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HRNR links:

FLG-AS1 (HGNC:):

FLG-AS1 links:

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

CCDST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006100327).

BP6

Variant 1-152218606-C-G is Benign according to our data. Variant chr1-152218606-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639207.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRNR	NM_001009931.3 link	c.3023G>C	p.Ser1008Thr	missense_variant	3/3	ENST00000368801.4	NP_001009931.1	Q86YZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRNR	ENST00000368801.4 link	c.3023G>C	p.Ser1008Thr	missense_variant	3/3	1	NM_001009931.3	ENSP00000357791.3		Q86YZ3

Frequencies

GnomAD3 genomes

AF:

0.000919

AC:

137

AN:

149044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00495

Gnomad FIN

AF:

0.00175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.000976

GnomAD3 exomes

AF:

0.00195

AC:

491

AN:

251428

Hom.:

AF XY:

0.00238

AC XY:

324

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00738

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00154

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00144

AC:

2109

AN:

1461718

Hom.:

Cov.:

128

AF XY:

0.00163

AC XY:

1182

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00425

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00740

Gnomad4 FIN exome

AF:

0.00140

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.000918

AC:

137

AN:

149166

Hom.:

Cov.:

AF XY:

0.000960

AC XY:

AN XY:

72886

show subpopulations

Gnomad4 AFR

AF:

0.000149

Gnomad4 AMR

AF:

0.0000664

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00495

Gnomad4 FIN

AF:

0.00175

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.000964

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.000725

ExAC

AF:

0.00194

AC:

236

EpiCase

AF:

0.00104

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

HRNR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.80

DEOGEN2

Benign

0.012

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.16

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.73

REVEL

Benign

0.087

Sift

Benign

0.56

Sift4G

Benign

0.64

Polyphen

0.96

Vest4

0.079

MVP

0.50

ClinPred

0.019

GERP RS

3.5

Varity_R

0.051

gMVP

0.0067

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