dbSNP rs904360907: CRIP2:p.Ala96Gly (chr14-105478821-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001312.4(CRIP2):c.287C>G(p.Ala96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,430,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.11089963).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRIP2	NM_001312.4	MANE Select	c.287C>G	p.Ala96Gly	missense	Exon 4 of 8	NP_001303.1	P52943-1
CRIP2	NM_001270837.2		c.509C>G	p.Ala170Gly	missense	Exon 4 of 8	NP_001257766.1	P52943-2
CRIP2	NM_001270841.2		c.44-304C>G		intron	N/A	NP_001257770.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRIP2	ENST00000329146.9	TSL:1 MANE Select	c.287C>G	p.Ala96Gly	missense	Exon 4 of 8	ENSP00000328521.5	P52943-1
CRIP2	ENST00000548309.1	TSL:1	n.1082C>G		non_coding_transcript_exon	Exon 4 of 8
CRIP2	ENST00000483017.7	TSL:2	c.509C>G	p.Ala170Gly	missense	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000460

AC:

AN:

43510

AF XY:

0.0000435

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1279166

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

623012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25722

American (AMR)

AF:

0.00

AC:

AN:

18434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18516

East Asian (EAS)

AF:

0.00

AC:

AN:

32798

South Asian (SAS)

AF:

0.00

AC:

AN:

62278

European-Finnish (FIN)

AF:

0.000485

AC:

AN:

30958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3596

European-Non Finnish (NFE)

AF:

0.0000416

AC:

AN:

1033814

Other (OTH)

AF:

0.000113

AC:

AN:

53050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151816

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67896

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000640

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.7

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.063

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.24

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.26

REVEL

Benign

0.041

Sift

Benign

0.096

Sift4G

Uncertain

0.056

Polyphen

0.018

Vest4

0.059

MutPred

0.26

Loss of stability (P = 0.0377)

MVP

0.63

MPC

0.28

ClinPred

0.026

GERP RS

-0.10

Varity_R

0.039

gMVP

0.26

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over