Variant 1-152213599-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.8030G>C(p.Arg2677Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000331 in 1,094,524 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 2 hom., cov: 10)

Exomes 𝑓: 0.00033 ( 65 hom. )

Failed GnomAD Quality Control

Consequence

HRNR
NM_001009931.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.25

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=0.005998373).

BP6

Variant 1-152213599-C-G is Benign according to our data. Variant chr1-152213599-C-G is described in ClinVar as [Benign]. Clinvar id is 2639196.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRNR	NM_001009931.3 link	c.8030G>C	p.Arg2677Pro	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.8030G>C	p.Arg2677Pro	missense_variant	3/3	1	NM_001009931.3	ENSP00000357791.3		Q86YZ3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

67742

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00693

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00215

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000608

Gnomad OTH

AF:

0.00129

GnomAD3 exomes

AF:

0.000890

AC:

AN:

95516

Hom.:

AF XY:

0.000898

AC XY:

AN XY:

52364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000192

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00195

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000271

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000331

AC:

362

AN:

1094524

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

210

AN XY:

549672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000974

Gnomad4 ASJ exome

AF:

0.00746

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000417

Gnomad4 OTH exome

AF:

0.000706

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000251

AC:

AN:

67800

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

32482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00693

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00217

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000608

Gnomad4 OTH

AF:

0.00126

Alfa

AF:

0.0000742

Hom.:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

HRNR: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.46

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.27

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

REVEL

Benign

0.046

Sift

Benign

0.041

Sift4G

Uncertain

0.053

Polyphen

0.62

Vest4

0.25

MutPred

0.29

Loss of MoRF binding (P = 2e-04);

MVP

0.29

ClinPred

0.025

GERP RS

-0.93

Varity_R

0.15

gMVP

0.037

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