NM_001312.4:c.241C>G

Variant names:

• chr14-105478775-C-G
• rs587625819
• NM_001312.4:c.241C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001312.4(CRIP2):​c.241C>G​(p.Leu81Val) 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. 16/22 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. L81M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRIP2 NM_001312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 0 publications found

Genes affected

CRIP2 (HGNC:2361): (cysteine rich protein 2) This gene encodes a putative transcription factor with two LIM zinc-binding domains. The encoded protein may participate in the differentiation of smooth muscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11966425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP2	NM_001312.4	MANE Select	c.241C>G	p.Leu81Val	missense	Exon 4 of 8	NP_001303.1	P52943-1
	CRIP2	NM_001270837.2		c.463C>G	p.Leu155Val	missense	Exon 4 of 8	NP_001257766.1	P52943-2
	CRIP2	NM_001270841.2		c.44-350C>G		intron	N/A	NP_001257770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP2	ENST00000329146.9	TSL:1 MANE Select	c.241C>G	p.Leu81Val	missense	Exon 4 of 8	ENSP00000328521.5	P52943-1
	CRIP2	ENST00000548309.1	TSL:1	n.1036C>G		non_coding_transcript_exon	Exon 4 of 8
	CRIP2	ENST00000483017.7	TSL:2	c.463C>G	p.Leu155Val	missense	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.65
DANN	Benign	0.93
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.17
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.054
Sift	Benign	0.25	T
Sift4G	Benign	0.47	T
Polyphen		0.0040	B
Vest4		0.078
MutPred		0.41		Gain of catalytic residue at Q86 (P = 2e-04)
MVP		0.61
MPC		0.24
ClinPred		0.039	T
GERP RS		-2.4
Varity_R		0.038
gMVP		0.24
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs587625819; hg19: chr14-105945112;