ENST00000533783.2:c.-195G>A

Variant names:

• chr11-19210527-C-T
• rs569978006
• ENST00000533783.2:c.-195G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The ENST00000533783.2(CSRP3):​c.-195G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 137,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSRP3 ENST00000533783.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.86
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00152 (209/137440) while in subpopulation NFE AF = 0.00228 (150/65844). AF 95% confidence interval is 0.00198. There are 1 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 209 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+13608C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP3	ENST00000533783.2	TSL:1	c.-195G>A		5_prime_UTR	Exon 1 of 7	ENSP00000431813.1	P50461-1
	CSRP3-AS1	ENST00000527978.2	TSL:5	n.145+13608C>T		intron	N/A
	CSRP3-AS1	ENST00000789312.1		n.106+602C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 209 AN: 137364 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.000655

Gnomad AMI AF: 0.00333

Gnomad AMR AF: 0.00178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000676

Gnomad FIN AF: 0.000144

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00328

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 82 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 50

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

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: 0.00 AC: 0 AN: 68

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.00152 AC: 209 AN: 137440 Hom.: 1 Cov.: 27 AF XY: 0.00146 AC XY: 95 AN XY: 65168

African (AFR) AF: 0.000654 AC: 24 AN: 36714

American (AMR) AF: 0.00177 AC: 22 AN: 12406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 4756

South Asian (SAS) AF: 0.000678 AC: 3 AN: 4424

European-Finnish (FIN) AF: 0.000144 AC: 1 AN: 6922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 224

European-Non Finnish (NFE) AF: 0.00228 AC: 150 AN: 65844

Other (OTH) AF: 0.00324 AC: 6 AN: 1850

Alfa AF: 0.0000531 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	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	-0.97
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-1.9
PromoterAI		0.0078	Neutral

Splicing

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

Other links and lift over

dbSNP: rs569978006; hg19: chr11-19232074;