14-90397108-G-T

Position:

• chr14-90397108-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_006888.6(CALM1):​c.-123G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,114,286 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (3 hom.)
• Consequence: CALM1 NM_006888.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 14-90397108-G-T is Benign according to our data. Variant chr14-90397108-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6	c.-123G>T		5_prime_UTR_variant	1/6	ENST00000356978.9
CALM1	NM_001363669.2	c.-106+450G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9	c.-123G>T		5_prime_UTR_variant	1/6	1	NM_006888.6	P1

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152168 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00224 AC: 2151 AN: 962000 Hom.: 3 Cov.: 12 AF XY: 0.00211 AC XY: 1034 AN XY: 489896

Gnomad4 AFR exome AF: 0.00925

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.000566

Gnomad4 EAS exome AF: 0.0000596

Gnomad4 SAS exome AF: 0.0000294

Gnomad4 FIN exome AF: 0.00287

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.00445 AC: 677 AN: 152286 Hom.: 1 Cov.: 34 AF XY: 0.00426 AC XY: 317 AN XY: 74448

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00204

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.00475

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

GeneDx

Oct 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.85
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs532682698; hg19: chr14-90863452;