14-90405134-T-C

Position:

• chr14-90405134-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006888.6(CALM1):​c.*417T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 167,722 control chromosomes in the GnomAD database, including 2,198 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 0.13 (2007 hom., cov: 33)
  • Exomes 𝑓: 0.12 (191 hom.)
• Consequence: CALM1 NM_006888.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

Genes affected

CALM1 (HGNC:1442): (calmodulin 1) This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. Two pseudogenes have been identified on chromosome 7 and X. Multiple transcript variants encoding different isoforms have been found for this gene.A missense mutation in the CALM1 gene has been associated with ventricular tachycardia.[provided by RefSeq, May 2020]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM1	NM_006888.6	c.*417T>C		3_prime_UTR_variant	6/6	ENST00000356978.9	NP_008819.1
CALM1	NM_001363669.2	c.*417T>C		3_prime_UTR_variant	6/6		NP_001350598.1
CALM1	NM_001363670.2	c.*417T>C		3_prime_UTR_variant	6/6		NP_001350599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978.9	c.*417T>C		3_prime_UTR_variant	6/6	1	NM_006888.6	ENSP00000349467	P1
	ENST00000555853.1	n.44+58A>G		intron_variant, non_coding_transcript_variant		3
CALM1	ENST00000553630.1	c.*508T>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	5		ENSP00000451646
CALM1	ENST00000544280.6			downstream_gene_variant		1		ENSP00000442853

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19742 AN: 152116 Hom.: 2010 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.115 AC: 1785 AN: 15488 Hom.: 191 Cov.: 0 AF XY: 0.114 AC XY: 915 AN XY: 8004

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0709

Gnomad4 NFE exome AF: 0.0798

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.130 AC: 19768 AN: 152234 Hom.: 2007 Cov.: 33 AF XY: 0.134 AC XY: 9989 AN XY: 74434

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.0801

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0914 Hom.: 297

Bravo AF: 0.140

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs5871; hg19: chr14-90871478;