3-39143393-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033027.4(CSRNP1):c.1432C>T(p.Leu478Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,614,168 control chromosomes in the GnomAD database, including 67 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 62 hom. )

Consequence

CSRNP1
NM_033027.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.650

Variant links:

Genes affected

CSRNP1 (HGNC:14300): (cysteine and serine rich nuclear protein 1) This gene encodes a protein that localizes to the nucleus and expression of this gene is induced in response to elevated levels of axin. The Wnt signalling pathway, which is negatively regulated by axin, is important in axis formation in early development and impaired regulation of this signalling pathway is often involved in tumors. A decreased level of expression of this gene in tumors compared to the level of expression in their corresponding normal tissues suggests that this gene product has a tumor suppressor function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CSRNP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002443254).

BP6

Variant 3-39143393-G-A is Benign according to our data. Variant chr3-39143393-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 156209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00671 (9813/1461804) while in subpopulation MID AF= 0.0258 (149/5766). AF 95% confidence interval is 0.0225. There are 62 homozygotes in gnomad4_exome. There are 5179 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRNP1	NM_033027.4 link	c.1432C>T	p.Leu478Phe	missense_variant	Exon 5 of 5	ENST00000273153.10	NP_149016.2	Q96S65A0A024R2U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRNP1	ENST00000273153.10 link	c.1432C>T	p.Leu478Phe	missense_variant	Exon 5 of 5	1	NM_033027.4	ENSP00000273153.5		Q96S65
CSRNP1	ENST00000514182.1 link	c.1432C>T	p.Leu478Phe	missense_variant	Exon 5 of 5	1		ENSP00000422532.1		Q96S65

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

737

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00582

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00651

AC:

1635

AN:

251020

Hom.:

AF XY:

0.00755

AC XY:

1025

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00651

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00671

AC:

9813

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

5179

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.000843

Gnomad4 NFE exome

AF:

0.00628

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.00484

AC:

737

AN:

152364

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00582

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00727

Hom.:

Bravo

AF:

0.00520

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00623

AC:

756

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.60

.;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.061

Sift

Benign

0.17

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

B;B

Vest4

0.029

MVP

0.17

MPC

0.28

ClinPred

0.0012

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.087

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

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