Genetic Variant CRIP2:p.Ser74Phe (chr14-105478755-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001312.4(CRIP2):c.221C>T(p.Ser74Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,432,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

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.221C>T	p.Ser74Phe	missense	Exon 4 of 8	NP_001303.1	P52943-1
CRIP2	NM_001270837.2		c.443C>T	p.Ser148Phe	missense	Exon 4 of 8	NP_001257766.1	P52943-2
CRIP2	NM_001270841.2		c.44-370C>T		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.221C>T	p.Ser74Phe	missense	Exon 4 of 8	ENSP00000328521.5	P52943-1
CRIP2	ENST00000548309.1	TSL:1	n.1016C>T		non_coding_transcript_exon	Exon 4 of 8
CRIP2	ENST00000483017.7	TSL:2	c.443C>T	p.Ser148Phe	missense	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151792

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:

0.000195

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000402

AC:

AN:

49812

AF XY:

0.00

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:

0.0000536

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1280324

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

621398

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27254

American (AMR)

AF:

0.00

AC:

AN:

19558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18580

East Asian (EAS)

AF:

0.0000294

AC:

AN:

34004

South Asian (SAS)

AF:

0.00

AC:

AN:

62596

European-Finnish (FIN)

AF:

0.0000323

AC:

AN:

31000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3564

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

1030674

Other (OTH)

AF:

0.0000188

AC:

AN:

53094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

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:

0.0000132

AC:

AN:

151898

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000196

AC:

AN:

5110

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67882

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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

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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

0.76

MutationAssessor

Uncertain

2.7

PhyloP100

3.2

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.60

MutPred

0.42

Gain of catalytic residue at A72 (P = 0)

MVP

0.98

MPC

0.85

ClinPred

0.86

GERP RS

4.0

Varity_R

0.60

gMVP

0.63

Mutation Taster

=45/55

disease causing

(source)

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

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