Genetic Variant CSRP3:c.-163_-162delAA (chr11-19210493-CTT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000533783.2(CSRP3):c.-163_-162delAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 98,990 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.063 ( 0 hom. )

Consequence

CSRP3
ENST00000533783.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

1 publications found

Variant links:

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 links:

CSRP3-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

CSRP3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0015 (148/98974) while in subpopulation EAS AF = 0.0141 (49/3470). AF 95% confidence interval is 0.011. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 148 AD,SD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533783.2. 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-AS1	NR_183675.1		n.207+13592_207+13593delTT		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSRP3	ENST00000533783.2	TSL:1	c.-163_-162delAA	5_prime_UTR	Exon 1 of 7	ENSP00000431813.1	P50461-1
CSRP3-AS1	ENST00000527978.2	TSL:5	n.145+13592_145+13593delTT	intron	N/A
CSRP3-AS1	ENST00000789312.1		n.106+586_106+587delTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

148

AN:

98994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000638

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00502

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00225

GnomAD4 exome

AF:

0.0625

AC:

AN:

Hom.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0625

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00150

AC:

148

AN:

98974

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

AN XY:

46650

show subpopulations

African (AFR)

AF:

0.000638

AC:

AN:

29796

American (AMR)

AF:

0.00123

AC:

AN:

8936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2442

East Asian (EAS)

AF:

0.0141

AC:

AN:

3470

South Asian (SAS)

AF:

0.00251

AC:

AN:

2790

European-Finnish (FIN)

AF:

0.00502

AC:

AN:

4382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

44966

Other (OTH)

AF:

0.00224

AC:

AN:

1338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.00

Hom.:

800

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Publications

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11-19210493-CTTTTTTTTT-CTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over