rs12539126

Positions:

• chr7-134750686-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417172.5(CALD1):​c.-130+6323T>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 ENST00000417172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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]

LOC124901750 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CALD1	XM_047420859.1	c.-130+5114T>C		intron_variant			XP_047276815.1
CALD1	XM_047420865.1	c.-130+5114T>C		intron_variant			XP_047276821.1
CALD1	XM_047420867.1	c.-130+5114T>C		intron_variant			XP_047276823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000417172.5	c.-130+6323T>C		intron_variant		5		ENSP00000398826.1
CALD1	ENST00000436461.6	c.-130+5114T>C		intron_variant		5		ENSP00000411476.2

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

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.139

Alfa AF: 0.154 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12539126; hg19: chr7-134435437;