rs7756992

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017774.3(CDKAL1):​c.371+30101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,020 control chromosomes in the GnomAD database, including 11,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.37 ( 11801 hom., cov: 32)

Consequence

CDKAL1
NM_017774.3 intron

Scores

2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.87
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.06).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKAL1NM_017774.3 linkc.371+30101A>G intron_variant Intron 5 of 15 ENST00000274695.8 NP_060244.2 Q5VV42-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKAL1ENST00000274695.8 linkc.371+30101A>G intron_variant Intron 5 of 15 1 NM_017774.3 ENSP00000274695.4 Q5VV42-1
CDKAL1ENST00000378610.1 linkc.371+30101A>G intron_variant Intron 3 of 13 2 ENSP00000367873.1 Q5VV42-1

Frequencies

GnomAD3 genomes
AF:
0.371
AC:
56381
AN:
151902
Hom.:
11781
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.563
Gnomad AMI
AF:
0.363
Gnomad AMR
AF:
0.311
Gnomad ASJ
AF:
0.316
Gnomad EAS
AF:
0.475
Gnomad SAS
AF:
0.273
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.310
Gnomad NFE
AF:
0.274
Gnomad OTH
AF:
0.346
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.371
AC:
56440
AN:
152020
Hom.:
11801
Cov.:
32
AF XY:
0.374
AC XY:
27767
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.563
AC:
0.563254
AN:
0.563254
Gnomad4 AMR
AF:
0.310
AC:
0.310462
AN:
0.310462
Gnomad4 ASJ
AF:
0.316
AC:
0.316138
AN:
0.316138
Gnomad4 EAS
AF:
0.474
AC:
0.474324
AN:
0.474324
Gnomad4 SAS
AF:
0.273
AC:
0.273067
AN:
0.273067
Gnomad4 FIN
AF:
0.350
AC:
0.350019
AN:
0.350019
Gnomad4 NFE
AF:
0.274
AC:
0.274253
AN:
0.274253
Gnomad4 OTH
AF:
0.346
AC:
0.3463
AN:
0.3463
Heterozygous variant carriers
0
1683
3366
5048
6731
8414
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
536
1072
1608
2144
2680
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.304
Hom.:
35644
Bravo
AF:
0.379
Asia WGS
AF:
0.351
AC:
1216
AN:
3472

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Type 2 diabetes mellitus Uncertain:1
Sep 01, 2014
OMIM
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.48
DANN
Benign
0.47
Mutation Taster
=100/0
polymorphism (auto)

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: rs7756992; hg19: chr6-20679709; API