1-152409971-C-T

Variant names:

• chr1-152409971-C-T
• NM_016190.3:c.1111G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016190.3(CRNN):​c.1111G>A​(p.Ala371Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CRNN NM_016190.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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 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=0.043438137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNN	NM_016190.3	c.1111G>A	p.Ala371Thr	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.1111G>A	p.Ala371Thr	missense_variant	Exon 3 of 3	1	NM_016190.3	ENSP00000271835.3
FLG-AS1	ENST00000411804.1	n.95-34873C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1111G>A (p.A371T) 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 1111, causing the alanine (A) at amino acid position 371 to be replaced by a threonine (T). 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	0.068
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.66
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.021
Sift	Benign	0.072	T
Sift4G	Benign	0.36	T
Polyphen		0.13	B
Vest4		0.024
MutPred		0.19		Gain of glycosylation at A371 (P = 0.0303);
MVP		0.040
MPC		0.067
ClinPred		0.047	T
GERP RS		-0.98
Varity_R		0.032
gMVP		0.064

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: chr1-152382447;