Genetic Variant NM_017774.3:c.1549-72G>A (chr6-21230776-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017774.3(CDKAL1):c.1549-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,214,854 control chromosomes in the GnomAD database, including 48,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 12942 hom., cov: 33)

Exomes 𝑓: 0.24 ( 35113 hom. )

Consequence

CDKAL1
NM_017774.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.975

Publications

8 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:

ENSG00000287404 (HGNC:):

ENSG00000287404 links:

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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3 link	c.1549-72G>A		intron_variant	Intron 15 of 15	ENST00000274695.8	NP_060244.2	Q5VV42-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8 link	c.1549-72G>A		intron_variant	Intron 15 of 15	1	NM_017774.3	ENSP00000274695.4		Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55128

AN:

151990

Hom.:

12897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.244

AC:

259272

AN:

1062748

Hom.:

35113

AF XY:

0.243

AC XY:

126809

AN XY:

520796

show subpopulations

African (AFR)

AF:

0.693

AC:

16998

AN:

24542

American (AMR)

AF:

0.315

AC:

7037

AN:

22352

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

3631

AN:

17464

East Asian (EAS)

AF:

0.277

AC:

9460

AN:

34160

South Asian (SAS)

AF:

0.290

AC:

13493

AN:

46498

European-Finnish (FIN)

AF:

0.256

AC:

11203

AN:

43830

Middle Eastern (MID)

AF:

0.263

AC:

858

AN:

3258

European-Non Finnish (NFE)

AF:

0.224

AC:

184801

AN:

825528

Other (OTH)

AF:

0.261

AC:

11791

AN:

45116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9171

18342

27514

36685

45856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6672

13344

20016

26688

33360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55226

AN:

152106

Hom.:

12942

Cov.:

AF XY:

0.364

AC XY:

27081

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.675

AC:

28006

AN:

41488

American (AMR)

AF:

0.340

AC:

5196

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

689

AN:

3468

East Asian (EAS)

AF:

0.230

AC:

1186

AN:

5158

South Asian (SAS)

AF:

0.300

AC:

1446

AN:

4818

European-Finnish (FIN)

AF:

0.273

AC:

2883

AN:

10570

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.219

AC:

14890

AN:

67994

Other (OTH)

AF:

0.336

AC:

712

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1549

3097

4646

6194

7743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.292

Hom.:

17630

Bravo

AF:

0.377

Asia WGS

AF:

0.331

AC:

1150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.033

(source)

DANN

Benign

0.54

PhyloP100

-0.97

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over