rs9465873

Positions:

• chr6-20733158-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.372-6361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,916 control chromosomes in the GnomAD database, including 26,172 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 0.58 (26172 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.372-6361G>A		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.372-6361G>A		intron_variant		1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.372-6361G>A		intron_variant		2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88612 AN: 151798 Hom.: 26165 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.584 AC: 88652 AN: 151916 Hom.: 26172 Cov.: 31 AF XY: 0.577 AC XY: 42801 AN XY: 74234

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.616

Alfa AF: 0.617 Hom.: 38872

Bravo AF: 0.596

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.44
DANN	Benign	0.22

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: rs9465873; hg19: chr6-20733389;