Variant 14-105478792-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001312.4(CRIP2):c.258G>C(p.Gln86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,434,282 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 14 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

Variant links:

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]

CRIP2 links:

CRIP2 (HGNC:):

CRIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063350797).

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIP2	NM_001312.4 linkuse as main transcript	c.258G>C	p.Gln86His	missense_variant	4/8	ENST00000329146.9	NP_001303.1	P52943-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIP2	ENST00000329146.9 linkuse as main transcript	c.258G>C	p.Gln86His	missense_variant	4/8	1	NM_001312.4	ENSP00000328521.5		P52943-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000889

AC:

AN:

48370

Hom.:

AF XY:

0.000993

AC XY:

AN XY:

25180

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.000591

GnomAD4 exome

AF:

0.00270

AC:

3467

AN:

1282216

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

1627

AN XY:

623770

show subpopulations

Gnomad4 AFR exome

AF:

0.000488

Gnomad4 AMR exome

AF:

0.0000520

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152066

Hom.:

Cov.:

AF XY:

0.000861

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.00118

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.258G>C (p.Q86H) alteration is located in exon 4 (coding exon 4) of the CRIP2 gene. This alteration results from a G to C substitution at nucleotide position 258, causing the glutamine (Q) at amino acid position 86 to be replaced by a histidine (H). 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

0.089

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.13

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.056

T;T

Polyphen

0.21

.;B

Vest4

0.052

MutPred

0.36

.;Gain of catalytic residue at L81 (P = 6e-04);

MVP

0.65

MPC

0.47

ClinPred

0.069

GERP RS

-0.090

Varity_R

0.052

gMVP

0.35

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