Genetic Variant CRIP1:p.Cys52Phe (chr14-105488350-G-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001311.5(CRIP1):c.155G>T(p.Cys52Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,613,476 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 34)

Exomes 𝑓: 0.0098 ( 129 hom. )

Consequence

CRIP1
NM_001311.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.01

Variant links:

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]

CRIP1 links:

ENSG00000257341 (HGNC:):

ENSG00000257341 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0149309635).

BP6

Variant 14-105488350-G-T is Benign according to our data. Variant chr14-105488350-G-T is described in ClinVar as [Benign]. Clinvar id is 770784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIP1	NM_001311.5 link	c.155G>T	p.Cys52Phe	missense_variant	Exon 4 of 6	ENST00000392531.4	NP_001302.1	P50238

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIP1	ENST00000392531.4 link	c.155G>T	p.Cys52Phe	missense_variant	Exon 4 of 6	2	NM_001311.5	ENSP00000376315.3		P50238
ENSG00000257341	ENST00000477724.6 link	n.155G>T		non_coding_transcript_exon_variant	Exon 3 of 7	4		ENSP00000455329.1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1524

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00915

AC:

2288

AN:

250106

Hom.:

AF XY:

0.00931

AC XY:

1263

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00270

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00967

GnomAD4 exome

AF:

0.00980

AC:

14321

AN:

1461152

Hom.:

129

Cov.:

AF XY:

0.00979

AC XY:

7118

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.0100

AC:

1524

AN:

152324

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

816

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0358

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00621

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00939

AC:

1139

EpiCase

AF:

0.0119

EpiControl

AF:

0.00895

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 30, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

0.0086

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

D;D;D

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Pathogenic

0.87

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-11

D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.97

D;D;D

Vest4

0.77

MVP

0.99

MPC

0.31

ClinPred

0.081

GERP RS

3.8

Varity_R

0.83

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over