rs138795800

Variant names:

• chr1-152409646-C-G
• NM_016190.3:c.1436G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-152409646-C-G
• chr1-152409646-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016190.3(CRNN):​c.1436G>C​(p.Arg479Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,766 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R479Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRNN NM_016190.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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]

FLG-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09561288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNN	NM_016190.3	c.1436G>C	p.Arg479Pro	missense_variant	Exon 3 of 3	ENST00000271835.3	NP_057274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRNN	ENST00000271835.3	c.1436G>C	p.Arg479Pro	missense_variant	Exon 3 of 3	1	NM_016190.3	ENSP00000271835.3
FLG-AS1	ENST00000411804.1	n.95-35198C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0050
DANN	Benign	0.76
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.14	T
Polyphen		0.80	P
Vest4		0.096
MutPred		0.18		Loss of helix (P = 0.0093);
MVP		0.081
MPC		0.089
ClinPred		0.73	D
GERP RS		-8.2
Varity_R		0.24
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152382122; COSMIC: COSV55121876; COSMIC: COSV55121876;