dbSNP rs1301487932: CRIP2:p.Ala95Val (chr14-105478818-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001312.4(CRIP2):c.284C>T(p.Ala95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,430,376 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 1 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06811389).

BP6

Variant 14-105478818-C-T is Benign according to our data. Variant chr14-105478818-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3497084.Status of the report is criteria_provided_single_submitter, 1 stars.

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.284C>T	p.Ala95Val	missense	Exon 4 of 8	NP_001303.1	P52943-1
CRIP2	NM_001270837.2		c.506C>T	p.Ala169Val	missense	Exon 4 of 8	NP_001257766.1	P52943-2
CRIP2	NM_001270841.2		c.44-307C>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.284C>T	p.Ala95Val	missense	Exon 4 of 8	ENSP00000328521.5	P52943-1
CRIP2	ENST00000548309.1	TSL:1	n.1079C>T		non_coding_transcript_exon	Exon 4 of 8
CRIP2	ENST00000483017.7	TSL:2	c.506C>T	p.Ala169Val	missense	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000232

AC:

AN:

43110

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000112

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:

0.00000704

AC:

AN:

1278518

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

622594

show subpopulations

African (AFR)

AF:

0.000156

AC:

AN:

25658

American (AMR)

AF:

0.0000543

AC:

AN:

18416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18522

East Asian (EAS)

AF:

0.00

AC:

AN:

32760

South Asian (SAS)

AF:

0.0000161

AC:

AN:

62224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3590

European-Non Finnish (NFE)

AF:

0.00000194

AC:

AN:

1033376

Other (OTH)

AF:

0.0000189

AC:

AN:

53014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000263

AC:

AN:

151858

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41350

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67912

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.063

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.9

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.058

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.41

PhyloP100

-1.3

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.050

REVEL

Benign

0.072

Sift

Benign

0.29

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.090

MutPred

0.49

Gain of relative solvent accessibility (P = 0.0483)

MVP

0.43

MPC

0.24

ClinPred

0.036

GERP RS

-2.0

Varity_R

0.023

gMVP

0.25

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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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