chr14-105488480-G-C

Variant names:

• chr14-105488480-G-C
• rs141808882
• NM_001311.5:c.203G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001311.5(CRIP1):​c.203G>C​(p.Arg68Pro) 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 1,455,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRIP1 NM_001311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

Genes affected

CRIP1 (HGNC:2360): (cysteine rich protein 1) Cysteine-rich intestinal protein (CRIP) belongs to the LIM/double zinc finger protein family, members of which include cysteine- and glycine-rich protein-1 (CSRP1; MIM 123876), rhombotin-1 (RBTN1; MIM 186921), rhombotin-2 (RBTN2; MIM 180385), and rhombotin-3 (RBTN3; MIM 180386). CRIP may be involved in intestinal zinc transport (Hempe and Cousins, 1991 [PubMed 1946385]).[supplied by OMIM, Mar 2008]

ENSG00000257341 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity CRIP1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001311.5. 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
	CRIP1	NM_001311.5	MANE Select	c.203G>C	p.Arg68Pro	missense	Exon 5 of 6	NP_001302.1	P50238

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP1	ENST00000392531.4	TSL:2 MANE Select	c.203G>C	p.Arg68Pro	missense	Exon 5 of 6	ENSP00000376315.3	P50238
	CRIP1	ENST00000330233.11	TSL:1	c.203G>C	p.Arg68Pro	missense	Exon 4 of 5	ENSP00000332449.7	P50238
	ENSG00000257341	ENST00000477724.6	TSL:4	n.203G>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000455329.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247746 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455830 Hom.: 0 Cov.: 37 AF XY: 0.00000276 AC XY: 2 AN XY: 723804

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109898

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.65	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.38	D
PhyloP100		2.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.52
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.88	P
Vest4		0.65
MutPred		0.43		Loss of methylation at R68 (P = 0.0033)
MVP		0.90
MPC		0.13
ClinPred		0.87	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.51
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141808882; hg19: chr14-105954817;