chr7-134779071-A-G

Variant names:

• chr7-134779071-A-G
• rs3807337
• NM_001438769.1:c.-129-64813A>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.-129-64813A>G variant causes a intron 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: CALD1 NM_001438769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 9 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=-0.84).
• 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 rank	MANE	Protein	UniProt
CALD1	NM_001438769.1	c.-129-64813A>G		intron_variant	Intron 1 of 14		NP_001425698.1
CALD1	NM_001438770.1	c.-129-64813A>G		intron_variant	Intron 2 of 15		NP_001425699.1
CALD1	NM_001438778.1	c.-129-64813A>G		intron_variant	Intron 1 of 13		NP_001425707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000417172.5	c.-130+34708A>G		intron_variant	Intron 1 of 13	5		ENSP00000398826.1
CALD1	ENST00000436461.6	c.-130+33499A>G		intron_variant	Intron 1 of 10	5		ENSP00000411476.2
ENSG00000286458	ENST00000772186.1	n.301+35593T>C		intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.152 AC: 6313 AN: 41476

American (AMR) AF: 0.499 AC: 7612 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1651 AN: 3460

East Asian (EAS) AF: 0.503 AC: 2598 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2297 AN: 4816

European-Finnish (FIN) AF: 0.460 AC: 4859 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29256 AN: 67968

Other (OTH) AF: 0.404 AC: 853 AN: 2112

Alfa AF: 0.414 Hom.: 17874

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
PhyloP100		-0.034
PromoterAI		0.056	Neutral
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: rs3807337; hg19: chr7-134463822; COSMIC: COSV62649660; COSMIC: COSV62649660;