1-152219403-G-A
Position:
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
NM_001009931.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.55
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]
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 | 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 | c.2226C>T | p.His742= | synonymous_variant | 3/3 | 1 | NM_001009931.3 | P1 | |
FLG-AS1 | ENST00000653548.1 | n.166-29492G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.719 AC: 109206AN: 151896Hom.: 40623 Cov.: 33
GnomAD3 genomes
AF:
AC:
109206
AN:
151896
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.708 AC: 178049AN: 251482Hom.: 66101 AF XY: 0.714 AC XY: 96991AN XY: 135916
GnomAD3 exomes
AF:
AC:
178049
AN:
251482
Hom.:
AF XY:
AC XY:
96991
AN XY:
135916
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.792 AC: 1158388AN: 1461872Hom.: 468667 Cov.: 96 AF XY: 0.788 AC XY: 573215AN XY: 727238
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1158388
AN:
1461872
Hom.:
Cov.:
96
AF XY:
AC XY:
573215
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.719 AC: 109269AN: 152014Hom.: 40652 Cov.: 33 AF XY: 0.710 AC XY: 52741AN XY: 74296
GnomAD4 genome
AF:
AC:
109269
AN:
152014
Hom.:
Cov.:
33
AF XY:
AC XY:
52741
AN XY:
74296
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1673
AN:
3478
EpiCase
AF:
EpiControl
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at