7-134753773-A-T

Variant names:

• chr7-134753773-A-T
• rs10488456
• ENST00000417172.5:c.-130+9410A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000417172.5(CALD1):​c.-130+9410A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CALD1 ENST00000417172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	XM_047420859.1	c.-130+8201A>T		intron_variant	Intron 1 of 13		XP_047276815.1
CALD1	XM_047420865.1	c.-130+8201A>T		intron_variant	Intron 1 of 14		XP_047276821.1
CALD1	XM_047420867.1	c.-130+8201A>T		intron_variant	Intron 1 of 14		XP_047276823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000417172.5	c.-130+9410A>T		intron_variant	Intron 1 of 13	5		ENSP00000398826.1
CALD1	ENST00000436461.6	c.-130+8201A>T		intron_variant	Intron 1 of 10	5		ENSP00000411476.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488456; hg19: chr7-134438524;