rs9460612

chr6-21230776-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC107986578 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.1549-72G>A		intron_variant		ENST00000274695.8
LOC107986578	XR_001744021.2	n.284C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1549-72G>A		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.1549-72G>A		intron_variant		2		P1
CDKAL1	ENST00000476517.1	n.247-72G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.261

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

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.336

Alfa AF: 0.254 Hom.: 7890

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9460612; hg19: chr6-21231007;