rs9460612

Variant names:

• chr6-21230776-G-A
• rs9460612
• NM_017774.3:c.1549-72G>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 8 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]

ENSG00000287404 (HGNC:):

ACMG classification

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	c.1549-72G>A		intron_variant	Intron 15 of 15	ENST00000274695.8	NP_060244.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55128 AN: 151990 Hom.: 12897 Cov.: 33

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

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

GnomAD4 genome AF: 0.363 AC: 55226 AN: 152106 Hom.: 12942 Cov.: 33 AF XY: 0.364 AC XY: 27081 AN XY: 74364

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: 85 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14890 AN: 67994

Other (OTH) AF: 0.336 AC: 712 AN: 2116

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
DANN	Benign	0.54
PhyloP100		-0.97
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: rs9460612; hg19: chr6-21231007;