rs12539126

Variant names:

• chr7-134750686-T-C
• rs12539126
• NM_001438769.1:c.-130+39089T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001438769.1(CALD1):​c.-130+39089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,176 control chromosomes in the GnomAD database, including 1,534 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1534 hom., cov: 31)
• Consequence: CALD1 NM_001438769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 1 publications found

Genes affected

CALD1 (HGNC:1441): (caldesmon 1) This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca(2+)-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca(2+)-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000286458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_001438769.1	c.-130+39089T>C		intron_variant	Intron 1 of 14		NP_001425698.1
CALD1	NM_001438770.1	c.-130+36501T>C		intron_variant	Intron 2 of 15		NP_001425699.1
CALD1	NM_001438778.1	c.-130+39089T>C		intron_variant	Intron 1 of 13		NP_001425707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000417172.5	c.-130+6323T>C		intron_variant	Intron 1 of 13	5		ENSP00000398826.1
CALD1	ENST00000436461.6	c.-130+5114T>C		intron_variant	Intron 1 of 10	5		ENSP00000411476.2
ENSG00000286458	ENST00000772186.1	n.302-7438A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19783 AN: 152058 Hom.: 1535 Cov.: 31

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19782 AN: 152176 Hom.: 1534 Cov.: 31 AF XY: 0.132 AC XY: 9797 AN XY: 74394

African (AFR) AF: 0.0482 AC: 2002 AN: 41548

American (AMR) AF: 0.116 AC: 1779 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.116 AC: 602 AN: 5180

South Asian (SAS) AF: 0.139 AC: 668 AN: 4822

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11851 AN: 67992

Other (OTH) AF: 0.139 AC: 294 AN: 2108

Alfa AF: 0.149 Hom.: 257

Bravo AF: 0.122

Asia WGS AF: 0.118 AC: 411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.49
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12539126; hg19: chr7-134435437;