rs12527222

Variant names:

• chr6-21183323-C-T
• rs12527222
• NM_017774.3:c.1300-14698C>T

Variant summary

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

The NM_017774.3(CDKAL1):​c.1300-14698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,260 control chromosomes in the GnomAD database, including 203 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 0.047 (203 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1300-14698C>T		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.1300-14698C>T		intron_variant	Intron 13 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1300-14698C>T		intron_variant	Intron 11 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7156 AN: 152142 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0470 AC: 7158 AN: 152260 Hom.: 203 Cov.: 32 AF XY: 0.0474 AC XY: 3530 AN XY: 74440

African (AFR) AF: 0.0486 AC: 2019 AN: 41536

American (AMR) AF: 0.0468 AC: 717 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3466

East Asian (EAS) AF: 0.105 AC: 541 AN: 5176

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4826

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2931 AN: 68024

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0456 Hom.: 48

Bravo AF: 0.0499

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		-0.34
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: rs12527222; hg19: chr6-21183554;