11-19210493-CTTTTTTTTT-CTTTTTT

Variant names:

• chr11-19210493-CTTT-C
• rs34865888
• ENST00000533783.2:c.-164_-162delAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The ENST00000533783.2(CSRP3):​c.-164_-162delAAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 98,982 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: CSRP3 ENST00000533783.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 1 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-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.125 (2/16) while in subpopulation NFE AF = 0.125 (2/16). AF 95% confidence interval is 0.0222. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

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+13591_207+13593delTTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP3	ENST00000533783.2	TSL:1	c.-164_-162delAAA		5_prime_UTR	Exon 1 of 7	ENSP00000431813.1	P50461-1
	CSRP3-AS1	ENST00000527978.2	TSL:5	n.145+13591_145+13593delTTT		intron	N/A
	CSRP3-AS1	ENST00000789312.1		n.106+585_106+587delTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 12 AN: 98986 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000672

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000224

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.125 AC: 2 AN: 16 Hom.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 2 AN: 16

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000121 AC: 12 AN: 98966 Hom.: 0 Cov.: 0 AF XY: 0.000150 AC XY: 7 AN XY: 46646

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

African (AFR) AF: 0.0000671 AC: 2 AN: 29802

American (AMR) AF: 0.000224 AC: 2 AN: 8932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2442

East Asian (EAS) AF: 0.00 AC: 0 AN: 3468

South Asian (SAS) AF: 0.00 AC: 0 AN: 2792

European-Finnish (FIN) AF: 0.00137 AC: 6 AN: 4374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000445 AC: 2 AN: 44966

Other (OTH) AF: 0.00 AC: 0 AN: 1336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000409227), which strongly suggests a high chance of mosaicism in these individuals.

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

Splicing

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

Other links and lift over

dbSNP: rs34865888; hg19: chr11-19232040;