Genetic Variant CDKAL1:c.371+30101A>G (chr6-20679478-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

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 cumulative frequency of 0.371 (AC=56,440) in the gnomAD database across 152,020 control chromosomes, including 11,801 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.557. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

Frequency

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

Consequence

CDKAL1
NM_017774.3 intron

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.87

Publications

308 publications found

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]

CDKAL1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017774.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5572 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.371+30101A>G		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.371+30101A>G	intron	N/A	ENSP00000274695.4	Q5VV42-1
CDKAL1	ENST00000946780.1		c.371+30101A>G	intron	N/A	ENSP00000616839.1
CDKAL1	ENST00000378610.1	TSL:2	c.371+30101A>G	intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56381

AN:

151902

Hom.:

11781

Cov.:

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.:

AF XY:

0.374

AC XY:

27767

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.563

AC:

23339

AN:

41436

American (AMR)

AF:

0.310

AC:

4742

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1097

AN:

3470

East Asian (EAS)

AF:

0.474

AC:

2457

AN:

5180

South Asian (SAS)

AF:

0.273

AC:

1314

AN:

4812

European-Finnish (FIN)

AF:

0.350

AC:

3699

AN:

10568

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18641

AN:

67970

Other (OTH)

AF:

0.346

AC:

730

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1683

3366

5048

6731

8414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.463

AC:

56805

AN:

122770

Turkish Variome

AF:

0.278

AC:

430

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.474

AC:

4246

AN:

8960

Hom.:

1038

ABraOM SABE-WGS-1171

AF:

0.328

AC:

769

AN:

2342

Hom.:

131

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.48

(source)

DANN

Benign

0.47

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over