chr6-20599397-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.287-49896C>T		intron_variant	Intron 4 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-49896C>T		intron_variant	Intron 4 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.287-49896C>T		intron_variant	Intron 2 of 13	2		ENSP00000367873.1

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

GnomAD3 exomes AF: 0.388 AC: 51101 AN: 131626 Hom.: 10576 AF XY: 0.385 AC XY: 27595 AN XY: 71726

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 SAS exome AF: 0.415

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

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.349

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.327

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9366357; hg19: chr6-20599628;