14-105478777-G-C

Variant names:

• chr14-105478777-G-C
• NM_001312.4:c.243G>C
• CRIP2 p.Leu81Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001312.4(CRIP2):​c.243G>C​(p.Leu81Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRIP2 NM_001312.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.019).
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.

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.243G>C	p.Leu81Leu	synonymous	Exon 4 of 8	NP_001303.1	P52943-1
	CRIP2	NM_001270837.2		c.465G>C	p.Leu155Leu	synonymous	Exon 4 of 8	NP_001257766.1	P52943-2
	CRIP2	NM_001270841.2		c.44-348G>C		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.243G>C	p.Leu81Leu	synonymous	Exon 4 of 8	ENSP00000328521.5	P52943-1
	CRIP2	ENST00000548309.1	TSL:1	n.1038G>C		non_coding_transcript_exon	Exon 4 of 8
	CRIP2	ENST00000483017.7	TSL:2	c.465G>C	p.Leu155Leu	synonymous	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.90
DANN	Benign	0.90
PhyloP100		-1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-105945114;