Variant chr1-152219403-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001009931.3(HRNR):c.2226C>T(p.His742=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,014 control chromosomes in the GnomAD database, including 40,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 40652 hom., cov: 33)

Exomes 𝑓: 0.79 ( 468667 hom. )

Failed GnomAD Quality Control

Consequence

HRNR
NM_001009931.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.55

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:27913): (cervical cancer associated DHX9 suppressive transcript)

FLG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-152219403-G-A is Benign according to our data. Variant chr1-152219403-G-A is described in ClinVar as [Benign]. Clinvar id is 1249194.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRNR	NM_001009931.3 linkuse as main transcript	c.2226C>T	p.His742=	synonymous_variant	3/3	ENST00000368801.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRNR	ENST00000368801.4 linkuse as main transcript	c.2226C>T	p.His742=	synonymous_variant	3/3	1	NM_001009931.3	P1
FLG-AS1	ENST00000653548.1 linkuse as main transcript	n.166-29492G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109206

AN:

151896

Hom.:

40623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.713

GnomAD3 exomes

AF:

0.708

AC:

178049

AN:

251482

Hom.:

66101

AF XY:

0.714

AC XY:

96991

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.542

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.826

Gnomad NFE exome

AF:

0.836

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.792

AC:

1158388

AN:

1461872

Hom.:

468667

Cov.:

AF XY:

0.788

AC XY:

573215

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.586

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.698

Gnomad4 EAS exome

AF:

0.390

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.828

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.747

GnomAD4 genome

AF:

0.719

AC:

109269

AN:

152014

Hom.:

40652

Cov.:

AF XY:

0.710

AC XY:

52741

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.590

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.818

Gnomad4 NFE

AF:

0.841

Gnomad4 OTH

AF:

0.718

Alfa

AF:

0.788

Hom.:

20389

Bravo

AF:

0.697

Asia WGS

AF:

0.481

AC:

1673

AN:

3478

EpiCase

AF:

0.825

EpiControl

AF:

0.829

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

GeneDx

Mar 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.83

DANN

Benign

0.70

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