NM_016190.3:c.814G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016190.3(CRNN):​c.814G>A​(p.Gly272Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CRNN
NM_016190.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.40
Variant links:
Genes affected
CRNN (HGNC:1230): (cornulin) This gene encodes a member of the "fused gene" family of proteins, which contain N-terminus EF-hand domains and multiple tandem peptide repeats. The encoded protein contains two EF-hand Ca2+ binding domains in its N-terminus and two glutamine- and threonine-rich 60 amino acid repeats in its C-terminus. This gene, also known as squamous epithelial heat shock protein 53, may play a role in the mucosal/epithelial immune response and epidermal differentiation. [provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028967798).
BP6
Variant 1-152410268-C-T is Benign according to our data. Variant chr1-152410268-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2395262.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRNNNM_016190.3 linkc.814G>A p.Gly272Ser missense_variant Exon 3 of 3 ENST00000271835.3 NP_057274.1 Q9UBG3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRNNENST00000271835.3 linkc.814G>A p.Gly272Ser missense_variant Exon 3 of 3 1 NM_016190.3 ENSP00000271835.3 Q9UBG3
FLG-AS1ENST00000411804.1 linkn.95-34576C>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251374
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
36
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000761
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 26, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.013
DANN
Benign
0.51
DEOGEN2
Benign
0.0015
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.029
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.43
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.24
N
REVEL
Benign
0.028
Sift
Benign
0.44
T
Sift4G
Benign
0.48
T
Polyphen
0.0010
B
Vest4
0.049
MVP
0.014
MPC
0.063
ClinPred
0.028
T
GERP RS
-3.0
Varity_R
0.025
gMVP
0.17

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.

Other links and lift over

dbSNP: rs140890124; hg19: chr1-152382744; API