Genetic Variant NM_004078.3:c.82A>G (chr1-201496222-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004078.3(CSRP1):c.82A>G(p.Asn28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,614,194 control chromosomes in the GnomAD database, including 5 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 Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

CSRP1
NM_004078.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

CSRP1 (HGNC:2469): (cysteine and glycine rich protein 1) This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

CSRP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009994537).

BP6

Variant 1-201496222-T-C is Benign according to our data. Variant chr1-201496222-T-C is described in ClinVar as [Benign]. Clinvar id is 720828.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP1	NM_004078.3 link	c.82A>G	p.Asn28Asp	missense_variant	Exon 2 of 6	ENST00000340006.7	NP_004069.1	P21291A0A384P5K2
CSRP1	NM_001193571.2 link	c.82A>G	p.Asn28Asp	missense_variant	Exon 2 of 6		NP_001180500.1	P21291A0A384P5K2
CSRP1	NM_001193572.2 link	c.82A>G	p.Asn28Asp	missense_variant	Exon 2 of 6		NP_001180501.1	P21291A0A384P5K2
CSRP1	NM_001193570.2 link	c.82A>G	p.Asn28Asp	missense_variant	Exon 2 of 6		NP_001180499.1	P21291B4DY28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP1	ENST00000340006.7 link	c.82A>G	p.Asn28Asp	missense_variant	Exon 2 of 6	1	NM_004078.3	ENSP00000345079.2		P21291

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

556

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000947

AC:

238

AN:

251442

Hom.:

AF XY:

0.000611

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000379

AC:

554

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00366

AC:

557

AN:

152352

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.00409

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00119

AC:

144

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T;T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.94

.;D;D;.;.

MetaRNN

Benign

0.010

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.94

L;L;.;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.047

D;D;D;D;D

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.0050

B;B;.;B;B

Vest4

0.25

MVP

0.83

MPC

0.26

ClinPred

0.013

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.46

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