7-134853124-C-T

Variant names:

• chr7-134853124-C-T
• rs3800737
• NM_033138.4:c.-42+9153C>T

Variant summary

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

The NM_033138.4(CALD1):​c.-42+9153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,088 control chromosomes in the GnomAD database, including 41,063 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 0.73 (41063 hom., cov: 31)
• Consequence: CALD1 NM_033138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033138.4. 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
	CALD1	NM_033138.4	MANE Select	c.-42+9153C>T		intron	N/A	NP_149129.2
	CALD1	NM_001438765.1		c.-42+9153C>T		intron	N/A	NP_001425694.1
	CALD1	NM_001438767.1		c.-42+9153C>T		intron	N/A	NP_001425696.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALD1	ENST00000361675.7	TSL:1 MANE Select	c.-42+9153C>T		intron	N/A	ENSP00000354826.2	Q05682-1
	CALD1	ENST00000361901.6	TSL:1	c.-42+9153C>T		intron	N/A	ENSP00000354513.2	Q05682-4
	CALD1	ENST00000866426.1		c.-42+9153C>T		intron	N/A	ENSP00000536485.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111140 AN: 151970 Hom.: 41052 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.731 AC: 111188 AN: 152088 Hom.: 41063 Cov.: 31 AF XY: 0.734 AC XY: 54539 AN XY: 74338

African (AFR) AF: 0.767 AC: 31807 AN: 41476

American (AMR) AF: 0.659 AC: 10074 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3466

East Asian (EAS) AF: 0.975 AC: 5045 AN: 5174

South Asian (SAS) AF: 0.721 AC: 3467 AN: 4810

European-Finnish (FIN) AF: 0.775 AC: 8199 AN: 10578

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48287 AN: 67986

Other (OTH) AF: 0.711 AC: 1504 AN: 2114

Alfa AF: 0.710 Hom.: 9045

Bravo AF: 0.724

Asia WGS AF: 0.814 AC: 2829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.075
DANN	Benign	0.75
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3800737; hg19: chr7-134537875;