rs45476991

Variant names:

• chr11-19188204-G-A
• rs45476991
• NM_003476.5:c.213C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-19188204-G-A
• chr11-19188204-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_003476.5(CSRP3):​c.213C>T​(p.Ile71Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,613,806 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (70 hom.)
• Consequence: CSRP3 NM_003476.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: 0.302
• Publications: 3 publications found

Genes affected

CSRP3 (HGNC:2472): (cysteine and glycine rich protein 3) This gene encodes a member of the CSRP family 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 protein is found in a group of proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Mutations in this gene are thought to cause heritable forms of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in humans. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

CSRP3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: SD, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• hypertrophic cardiomyopathy 12

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy 1M

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 11-19188204-G-A is Benign according to our data. Variant chr11-19188204-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.302 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00489 (744/152264) while in subpopulation NFE AF = 0.00769 (523/68016). AF 95% confidence interval is 0.00714. There are 1 homozygotes in GnomAd4. There are 324 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 744 AD,SD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003476.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP3	NM_003476.5	MANE Select	c.213C>T	p.Ile71Ile	synonymous	Exon 3 of 6	NP_003467.1	A2TDB8
	CSRP3	NM_001369404.1		c.113-1856C>T		intron	N/A	NP_001356333.1	A0A3B3ISZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP3	ENST00000265968.9	TSL:1 MANE Select	c.213C>T	p.Ile71Ile	synonymous	Exon 3 of 6	ENSP00000265968.3	P50461-1
	CSRP3	ENST00000533783.2	TSL:1	c.213C>T	p.Ile71Ile	synonymous	Exon 4 of 7	ENSP00000431813.1	P50461-1
	CSRP3	ENST00000951070.1		c.222C>T	p.Ile74Ile	synonymous	Exon 3 of 6	ENSP00000621129.1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00769

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00505 AC: 1268 AN: 251298 AF XY: 0.00498

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00457

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00795

Gnomad NFE exome AF: 0.00743

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00787 AC: 11498 AN: 1461542 Hom.: 70 Cov.: 32 AF XY: 0.00757 AC XY: 5501 AN XY: 727062

African (AFR) AF: 0.00119 AC: 40 AN: 33476

American (AMR) AF: 0.00141 AC: 63 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00390 AC: 102 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00321 AC: 277 AN: 86230

European-Finnish (FIN) AF: 0.00653 AC: 349 AN: 53406

Middle Eastern (MID) AF: 0.000363 AC: 2 AN: 5510

European-Non Finnish (NFE) AF: 0.00917 AC: 10197 AN: 1112002

Other (OTH) AF: 0.00774 AC: 467 AN: 60358

GnomAD4 genome AF: 0.00489 AC: 744 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74440

African (AFR) AF: 0.00128 AC: 53 AN: 41552

American (AMR) AF: 0.00137 AC: 21 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4816

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00769 AC: 523 AN: 68016

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00634 Hom.: 2

Bravo AF: 0.00465

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00840

EpiControl AF: 0.00693

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	4	not provided (4)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated cardiomyopathy 1M;C2677491:Hypertrophic cardiomyopathy 12 (1)
-	-	1	Hypertrophic cardiomyopathy 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.8
DANN	Benign	0.83
PhyloP100		0.30
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs45476991; hg19: chr11-19209751; COSMIC: COSV56390654;