chr7-134805711-C-T

Variant names:

• chr7-134805711-C-T
• rs17169635
• NM_033138.4:c.-130+25962C>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.-130+25962C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 144,680 control chromosomes in the GnomAD database, including 28,015 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 0.63 (28015 hom., cov: 31)
• Consequence: CALD1 NM_033138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_033138.4	c.-130+25962C>T		intron_variant	Intron 1 of 14	ENST00000361675.7	NP_149129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7	c.-130+25962C>T		intron_variant	Intron 1 of 14	1	NM_033138.4	ENSP00000354826.2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 91434 AN: 144566 Hom.: 27986 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.632 AC: 91510 AN: 144680 Hom.: 28015 Cov.: 31 AF XY: 0.633 AC XY: 44858 AN XY: 70834

African (AFR) AF: 0.607 AC: 23122 AN: 38084

American (AMR) AF: 0.577 AC: 8430 AN: 14604

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 1900 AN: 3258

East Asian (EAS) AF: 0.916 AC: 4730 AN: 5166

South Asian (SAS) AF: 0.532 AC: 2466 AN: 4636

European-Finnish (FIN) AF: 0.688 AC: 7159 AN: 10402

Middle Eastern (MID) AF: 0.486 AC: 135 AN: 278

European-Non Finnish (NFE) AF: 0.641 AC: 41865 AN: 65360

Other (OTH) AF: 0.613 AC: 1225 AN: 1998

Alfa AF: 0.609 Hom.: 12500

Bravo AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-1.3
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: rs17169635; hg19: chr7-134490462;