chr14-90397070-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_006888.6(CALM1):​c.-161C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 692,668 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 16 hom., cov: 34)
Exomes 𝑓: 0.00083 ( 5 hom. )

Consequence

CALM1
NM_006888.6 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.253
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 14-90397070-C-T is Benign according to our data. Variant chr14-90397070-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219590.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1131/152166) while in subpopulation AFR AF= 0.0256 (1062/41534). AF 95% confidence interval is 0.0243. There are 16 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1131 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CALM1NM_006888.6 linkuse as main transcriptc.-161C>T 5_prime_UTR_premature_start_codon_gain_variant 1/6 ENST00000356978.9 NP_008819.1 P0DP23P0DP24P0DP25B4DJ51
CALM1NM_006888.6 linkuse as main transcriptc.-161C>T 5_prime_UTR_variant 1/6 ENST00000356978.9 NP_008819.1 P0DP23P0DP24P0DP25B4DJ51
CALM1NM_001363669.2 linkuse as main transcriptc.-106+412C>T intron_variant NP_001350598.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CALM1ENST00000356978.9 linkuse as main transcriptc.-161C>T 5_prime_UTR_premature_start_codon_gain_variant 1/61 NM_006888.6 ENSP00000349467.4 P0DP23
CALM1ENST00000356978.9 linkuse as main transcriptc.-161C>T 5_prime_UTR_variant 1/61 NM_006888.6 ENSP00000349467.4 P0DP23

Frequencies

GnomAD3 genomes
AF:
0.00739
AC:
1124
AN:
152048
Hom.:
16
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0255
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
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:
0.0000883
Gnomad OTH
AF:
0.00573
GnomAD4 exome
AF:
0.000834
AC:
451
AN:
540502
Hom.:
5
Cov.:
7
AF XY:
0.000649
AC XY:
187
AN XY:
288180
show subpopulations
Gnomad4 AFR exome
AF:
0.0254
Gnomad4 AMR exome
AF:
0.00154
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000268
Gnomad4 OTH exome
AF:
0.00160
GnomAD4 genome
AF:
0.00743
AC:
1131
AN:
152166
Hom.:
16
Cov.:
34
AF XY:
0.00718
AC XY:
534
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0256
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00567
Bravo
AF:
0.00859
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
8.4
DANN
Benign
0.89
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141007341; hg19: chr14-90863414; API