rs9465994

Variant names:

• chr6-21201262-G-A
• rs9465994
• NM_017774.3:c.1536G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.1536G>A	p.Ser512Ser	synonymous	Exon 15 of 16	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1536G>A	p.Ser512Ser	synonymous	Exon 15 of 16	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.1644G>A	p.Ser548Ser	synonymous	Exon 16 of 17	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.1536G>A	p.Ser512Ser	synonymous	Exon 13 of 14	ENSP00000367873.1	Q5VV42-1

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

GnomAD2 exomes AF: 0.473 AC: 118654 AN: 251014 AF XY: 0.456

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 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

African (AFR) AF: 0.782 AC: 26113 AN: 33398

American (AMR) AF: 0.568 AC: 25357 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10153 AN: 26032

East Asian (EAS) AF: 0.440 AC: 17405 AN: 39514

South Asian (SAS) AF: 0.311 AC: 26706 AN: 85778

European-Finnish (FIN) AF: 0.437 AC: 23311 AN: 53292

Middle Eastern (MID) AF: 0.417 AC: 2398 AN: 5750

European-Non Finnish (NFE) AF: 0.473 AC: 522581 AN: 1105712

Other (OTH) AF: 0.470 AC: 28218 AN: 60028

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

African (AFR) AF: 0.764 AC: 31705 AN: 41474

American (AMR) AF: 0.559 AC: 8537 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2088 AN: 5150

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4812

European-Finnish (FIN) AF: 0.442 AC: 4656 AN: 10536

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31899 AN: 67966

Other (OTH) AF: 0.546 AC: 1150 AN: 2106

Alfa AF: 0.489 Hom.: 20472

Bravo AF: 0.571

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.042
DANN	Benign	0.50
PhyloP100		-1.7
Mutation Taster		=98/2	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: rs9465994; hg19: chr6-21201493; COSMIC: COSV51181132;