rs3807337

chr7-134779071-A-Gchr7-134779071-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007060537.1(LOC124901750):n.29221+35593T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,030 control chromosomes in the GnomAD database, including 11,718 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 0.37 (11718 hom., cov: 32)
• Consequence: LOC124901750 XR_007060537.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

Genes affected

LOC124901750 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901750	XR_007060537.1	n.29221+35593T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALD1	ENST00000417172.5	c.-130+34708A>G		intron_variant		5		P1
CALD1	ENST00000436461.6	c.-130+33499A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55848 AN: 151912 Hom.: 11723 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.367 AC: 55849 AN: 152030 Hom.: 11718 Cov.: 32 AF XY: 0.372 AC XY: 27653 AN XY: 74308

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.404

Alfa AF: 0.424 Hom.: 14165

Bravo AF: 0.359

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3807337; hg19: chr7-134463822; COSMIC: COSV62649660; COSMIC: COSV62649660;