Variant 1-152218471-C-T 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.3158G>A(p.Arg1053Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,612,842 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0051 ( 21 hom. )

Consequence

HRNR
NM_001009931.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.264

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=0.005783081).

BP6

Variant 1-152218471-C-T is Benign according to our data. Variant chr1-152218471-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639206.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3 link	c.3158G>A	p.Arg1053Gln	missense_variant	Exon 3 of 3	ENST00000368801.4	NP_001009931.1	Q86YZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRNR	ENST00000368801.4 link	c.3158G>A	p.Arg1053Gln	missense_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3		Q86YZ3

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

568

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00105

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00704

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00360

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.00822

GnomAD3 exomes

AF:

0.00302

AC:

760

AN:

251414

Hom.:

AF XY:

0.00302

AC XY:

410

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00453

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00506

AC:

7391

AN:

1461748

Hom.:

Cov.:

122

AF XY:

0.00485

AC XY:

3524

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.00604

Gnomad4 OTH exome

AF:

0.00464

GnomAD4 genome

AF:

0.00376

AC:

568

AN:

151094

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

273

AN XY:

73814

show subpopulations

Gnomad4 AFR

AF:

0.00105

Gnomad4 AMR

AF:

0.00703

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00360

Gnomad4 NFE

AF:

0.00528

Gnomad4 OTH

AF:

0.00813

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.00370

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00617

AC:

ExAC

AF:

0.00256

AC:

311

EpiCase

AF:

0.00442

EpiControl

AF:

0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HRNR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

DANN

Benign

0.64

DEOGEN2

Benign

0.014

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00011

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.76

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.14

REVEL

Benign

0.012

Sift

Benign

0.16

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.047

MVP

0.19

ClinPred

0.0012

GERP RS

-2.6

Varity_R

0.024

gMVP

0.0097

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