rs9465994

Positions:

• chr6-21201262-G-A
• chr6-21201262-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017774.3(CDKAL1):​c.1536G>A​(p.Ser512Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,606,118 control chromosomes in the GnomAD database, including 187,912 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 0.55 (24434 hom., cov: 32)
  • Exomes 𝑓: 0.47 (163478 hom.)
• Consequence: CDKAL1 NM_017774.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

CDKAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1536G>A	p.Ser512Ser	synonymous_variant	15/16	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1536G>A	p.Ser512Ser	synonymous_variant	15/16	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1536G>A	p.Ser512Ser	synonymous_variant	13/14	2		ENSP00000367873.1
CDKAL1	ENST00000476517.1	n.234G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83282 AN: 151882 Hom.: 24389 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.548

GnomAD3 exomes AF: 0.473 AC: 118654 AN: 251014 Hom.: 29599 AF XY: 0.456 AC XY: 61842 AN XY: 135668

Gnomad AFR exome AF: 0.774

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.400

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.470

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.469 AC: 682242 AN: 1454118 Hom.: 163478 Cov.: 38 AF XY: 0.462 AC XY: 333493 AN XY: 722036

Gnomad4 AFR exome AF: 0.782

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.549 AC: 83389 AN: 152000 Hom.: 24434 Cov.: 32 AF XY: 0.540 AC XY: 40135 AN XY: 74276

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.546

Alfa AF: 0.484 Hom.: 17652

Bravo AF: 0.571

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.042
DANN	Benign	0.50

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: rs9465994; hg19: chr6-21201493; COSMIC: COSV51181132;