7-134933849-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_033138.4(CALD1):c.1080A>G(p.Lys360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CALD1 NM_033138.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-134933849-A-G is Benign according to our data. Variant chr7-134933849-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 759456.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.61 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALD1	NM_033138.4	c.1080A>G	p.Lys360=	synonymous_variant	5/15	ENST00000361675.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALD1	ENST00000361675.7	c.1080A>G	p.Lys360=	synonymous_variant	5/15	1	NM_033138.4
	ENST00000665703.1	n.71+64234T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 148328 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000385 AC: 56 AN: 1454182 Hom.: 0 Cov.: 34 AF XY: 0.0000360 AC XY: 26 AN XY: 722880

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000921

Gnomad4 ASJ exome AF: 0.000231

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000307

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000539 AC: 8 AN: 148328 Hom.: 0 Cov.: 31 AF XY: 0.0000553 AC XY: 4 AN XY: 72342

Gnomad4 AFR AF: 0.000125

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000239 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.54
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs529198474; hg19: chr7-134618600; COSMIC: COSV62652232; COSMIC: COSV62652232;