rs4712569

Variant names:

• chr6-20939149-G-A
• rs4712569
• NM_017774.3:c.743-16270G>A

Variant summary

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

The NM_017774.3(CDKAL1):​c.743-16270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,116 control chromosomes in the GnomAD database, including 50,501 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 0.81 (50501 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.743-16270G>A		intron_variant	Intron 9 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.743-16270G>A		intron_variant	Intron 9 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.743-16270G>A		intron_variant	Intron 7 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123265 AN: 151998 Hom.: 50465 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.811 AC: 123354 AN: 152116 Hom.: 50501 Cov.: 32 AF XY: 0.816 AC XY: 60657 AN XY: 74380

African (AFR) AF: 0.707 AC: 29326 AN: 41498

American (AMR) AF: 0.832 AC: 12706 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2678 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5145 AN: 5178

South Asian (SAS) AF: 0.939 AC: 4530 AN: 4826

European-Finnish (FIN) AF: 0.867 AC: 9176 AN: 10588

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57116 AN: 67966

Other (OTH) AF: 0.814 AC: 1718 AN: 2110

Alfa AF: 0.829 Hom.: 13906

Bravo AF: 0.800

Asia WGS AF: 0.924 AC: 3214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.47
PhyloP100		-0.18
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: rs4712569; hg19: chr6-20939380;