rs3800748

Variant names:

• chr7-134865368-C-T
• rs3800748
• NM_033138.4:c.-41-2325C>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.-41-2325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,826 control chromosomes in the GnomAD database, including 4,086 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 0.21 (4086 hom., cov: 29)
• Consequence: CALD1 NM_033138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_033138.4	c.-41-2325C>T		intron_variant	Intron 2 of 14	ENST00000361675.7	NP_149129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7	c.-41-2325C>T		intron_variant	Intron 2 of 14	1	NM_033138.4	ENSP00000354826.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31424 AN: 151708 Hom.: 4083 Cov.: 29

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.207 AC: 31442 AN: 151826 Hom.: 4086 Cov.: 29 AF XY: 0.201 AC XY: 14877 AN XY: 74198

African (AFR) AF: 0.371 AC: 15323 AN: 41352

American (AMR) AF: 0.116 AC: 1775 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.177 AC: 908 AN: 5134

South Asian (SAS) AF: 0.175 AC: 837 AN: 4782

European-Finnish (FIN) AF: 0.0907 AC: 959 AN: 10574

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10556 AN: 67920

Other (OTH) AF: 0.172 AC: 363 AN: 2106

Alfa AF: 0.169 Hom.: 1613

Bravo AF: 0.214

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.022
DANN	Benign	0.58
PhyloP100		-3.0
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: rs3800748; hg19: chr7-134550119;