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GeneBe

6-20649303-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_017774.3(CDKAL1):c.297C>T(p.Ser99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,604,668 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

CDKAL1
NM_017774.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.167
Variant links:
Genes affected
CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-20649303-C-T is Benign according to our data. Variant chr6-20649303-C-T is described in ClinVar as [Benign]. Clinvar id is 776114.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.167 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00178 (270/152034) while in subpopulation EAS AF= 0.0365 (189/5178). AF 95% confidence interval is 0.0322. There are 7 homozygotes in gnomad4. There are 154 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDKAL1NM_017774.3 linkuse as main transcriptc.297C>T p.Ser99= synonymous_variant 5/16 ENST00000274695.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDKAL1ENST00000274695.8 linkuse as main transcriptc.297C>T p.Ser99= synonymous_variant 5/161 NM_017774.3 P1Q5VV42-1
CDKAL1ENST00000378610.1 linkuse as main transcriptc.297C>T p.Ser99= synonymous_variant 3/142 P1Q5VV42-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00178
AC:
271
AN:
151920
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0364
Gnomad SAS
AF:
0.00249
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00326
AC:
798
AN:
244902
Hom.:
17
AF XY:
0.00306
AC XY:
406
AN XY:
132570
show subpopulations
Gnomad AFR exome
AF:
0.000813
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0406
Gnomad SAS exome
AF:
0.00143
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000356
Gnomad OTH exome
AF:
0.00135
GnomAD4 exome
AF:
0.00113
AC:
1638
AN:
1452634
Hom.:
28
Cov.:
28
AF XY:
0.00109
AC XY:
786
AN XY:
722824
show subpopulations
Gnomad4 AFR exome
AF:
0.000272
Gnomad4 AMR exome
AF:
0.0000472
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0335
Gnomad4 SAS exome
AF:
0.00144
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000226
Gnomad4 OTH exome
AF:
0.00263
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00178
AC:
270
AN:
152034
Hom.:
7
Cov.:
33
AF XY:
0.00207
AC XY:
154
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00116
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0365
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000951
Alfa
AF:
0.000601
Hom.:
0
Bravo
AF:
0.00197
Asia WGS
AF:
0.0130
AC:
46
AN:
3472
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
5.6
Dann
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs9350269; hg19: chr6-20649534; COSMIC: COSV51196178; API