rs12055489

Variant names:

• chr6-21127833-A-G
• rs12055489
• NM_017774.3:c.1299+19370A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.1299+19370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 152,298 control chromosomes in the GnomAD database, including 378 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 0.031 (378 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1299+19370A>G		intron_variant	Intron 13 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+19370A>G		intron_variant	Intron 13 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1299+19370A>G		intron_variant	Intron 11 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4697 AN: 152180 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0309 AC: 4711 AN: 152298 Hom.: 378 Cov.: 32 AF XY: 0.0332 AC XY: 2469 AN XY: 74476

African (AFR) AF: 0.0298 AC: 1241 AN: 41576

American (AMR) AF: 0.0733 AC: 1121 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1699 AN: 5174

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4820

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00442 AC: 301 AN: 68032

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0328 Hom.: 154

Bravo AF: 0.0401

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		0.26
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

Other links and lift over

dbSNP: rs12055489; hg19: chr6-21128064; COSMIC: COSV107286141;