rs9460521

Variant names:

• chr6-20567310-G-A
• rs9460521
• NM_017774.3:c.286+18605G>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.286+18605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 151,576 control chromosomes in the GnomAD database, including 364 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 0.039 (364 hom., cov: 30)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.286+18605G>A		intron_variant	Intron 4 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.286+18605G>A		intron_variant	Intron 4 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.286+18605G>A		intron_variant	Intron 2 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5890 AN: 151462 Hom.: 362 Cov.: 30

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0000955

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00183

Gnomad OTH AF: 0.0332

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

GnomAD4 genome AF: 0.0390 AC: 5906 AN: 151576 Hom.: 364 Cov.: 30 AF XY: 0.0382 AC XY: 2831 AN XY: 74104

African (AFR) AF: 0.129 AC: 5340 AN: 41312

American (AMR) AF: 0.0160 AC: 244 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3462

East Asian (EAS) AF: 0.00118 AC: 6 AN: 5104

South Asian (SAS) AF: 0.0213 AC: 102 AN: 4794

European-Finnish (FIN) AF: 0.0000955 AC: 1 AN: 10476

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00183 AC: 124 AN: 67848

Other (OTH) AF: 0.0329 AC: 69 AN: 2100

Alfa AF: 0.0371 Hom.: 250

Bravo AF: 0.0436

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.44
DANN	Benign	0.53
PhyloP100		-0.11
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: rs9460521; hg19: chr6-20567541;