6-20599397-C-T

Variant names:

• chr6-20599397-C-T
• rs9366357
• NM_017774.3:c.287-49896C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.287-49896C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 449,568 control chromosomes in the GnomAD database, including 30,693 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 0.33 (8990 hom., cov: 32)
  • Exomes 𝑓: 0.37 (21703 hom.)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 14 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]

LOC105374968 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 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.287-49896C>T		intron	N/A	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.287-49896C>T		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.287-49896C>T		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.287-49896C>T		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50316 AN: 151842 Hom.: 8977 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.388 AC: 51101 AN: 131626 AF XY: 0.385

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.530

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.371 AC: 110338 AN: 297610 Hom.: 21703 Cov.: 0 AF XY: 0.375 AC XY: 63643 AN XY: 169666

African (AFR) AF: 0.206 AC: 1758 AN: 8528

American (AMR) AF: 0.498 AC: 13162 AN: 26442

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 3481 AN: 10530

East Asian (EAS) AF: 0.538 AC: 4900 AN: 9112

South Asian (SAS) AF: 0.418 AC: 24270 AN: 58072

European-Finnish (FIN) AF: 0.441 AC: 5475 AN: 12422

Middle Eastern (MID) AF: 0.372 AC: 1026 AN: 2760

European-Non Finnish (NFE) AF: 0.330 AC: 51395 AN: 155788

Other (OTH) AF: 0.349 AC: 4871 AN: 13956

GnomAD4 genome AF: 0.331 AC: 50363 AN: 151958 Hom.: 8990 Cov.: 32 AF XY: 0.343 AC XY: 25476 AN XY: 74260

African (AFR) AF: 0.230 AC: 9533 AN: 41488

American (AMR) AF: 0.397 AC: 6053 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1164 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2763 AN: 5166

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4820

European-Finnish (FIN) AF: 0.471 AC: 4967 AN: 10538

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22659 AN: 67918

Other (OTH) AF: 0.327 AC: 686 AN: 2100

Alfa AF: 0.337 Hom.: 2584

Bravo AF: 0.319

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9366357; hg19: chr6-20599628;