7-134753773-A-G

Variant names:

• chr7-134753773-A-G
• rs10488456
• NM_001438769.1:c.-130+42176A>G

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+42176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,008 control chromosomes in the GnomAD database, including 2,781 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 0.19 (2781 hom., cov: 32)
• Consequence: CALD1 NM_001438769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438769.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALD1	NM_001438769.1		c.-130+42176A>G		intron	N/A	NP_001425698.1
	CALD1	NM_001438770.1		c.-130+39588A>G		intron	N/A	NP_001425699.1
	CALD1	NM_001438778.1		c.-130+42176A>G		intron	N/A	NP_001425707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALD1	ENST00000417172.5	TSL:5	c.-130+9410A>G		intron	N/A	ENSP00000398826.1
	CALD1	ENST00000436461.6	TSL:5	c.-130+8201A>G		intron	N/A	ENSP00000411476.2
	ENSG00000286458	ENST00000772186.1		n.302-10525T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28316 AN: 151890 Hom.: 2780 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.186 AC: 28325 AN: 152008 Hom.: 2781 Cov.: 32 AF XY: 0.187 AC XY: 13908 AN XY: 74318

African (AFR) AF: 0.229 AC: 9488 AN: 41430

American (AMR) AF: 0.143 AC: 2183 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3466

East Asian (EAS) AF: 0.148 AC: 767 AN: 5176

South Asian (SAS) AF: 0.175 AC: 842 AN: 4810

European-Finnish (FIN) AF: 0.193 AC: 2044 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12015 AN: 67968

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.177 Hom.: 7798

Bravo AF: 0.188

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		-0.20
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: rs10488456; hg19: chr7-134438524;