1-152410178-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016190.3(CRNN):​c.904G>A​(p.Val302Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,608,038 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CRNN
NM_016190.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.75
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031371474).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRNNNM_016190.3 linkc.904G>A p.Val302Met 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.904G>A p.Val302Met missense_variant Exon 3 of 3 1 NM_016190.3 ENSP00000271835.3 Q9UBG3
FLG-AS1ENST00000411804.1 linkn.95-34666C>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.0000342
AC:
5
AN:
146344
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000207
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000495
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251416
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461694
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000342
AC:
5
AN:
146344
Hom.:
0
Cov.:
30
AF XY:
0.0000563
AC XY:
4
AN XY:
71044
show subpopulations
Gnomad4 AFR
AF:
0.0000257
Gnomad4 AMR
AF:
0.000207
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000495
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.904G>A (p.V302M) alteration is located in exon 3 (coding exon 2) of the CRNN gene. This alteration results from a G to A substitution at nucleotide position 904, causing the valine (V) at amino acid position 302 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.0080
DANN
Benign
0.51
DEOGEN2
Benign
0.00085
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0011
N
LIST_S2
Benign
0.22
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.031
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.15
N
REVEL
Benign
0.091
Sift
Benign
0.64
T
Sift4G
Benign
0.37
T
Polyphen
0.0020
B
Vest4
0.040
MutPred
0.26
Loss of sheet (P = 0.0457);
MVP
0.061
MPC
0.063
ClinPred
0.015
T
GERP RS
-7.9
Varity_R
0.022
gMVP
0.14

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: rs201228418; hg19: chr1-152382654; API