rs9465982

Positions:

• chr6-21178051-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.1300-19970T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,850 control chromosomes in the GnomAD database, including 20,485 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 0.51 (20485 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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 (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.1300-19970T>C		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1300-19970T>C		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.1300-19970T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77521 AN: 151732 Hom.: 20449 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.511 AC: 77616 AN: 151850 Hom.: 20485 Cov.: 32 AF XY: 0.507 AC XY: 37595 AN XY: 74196

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.527

Alfa AF: 0.495 Hom.: 4812

Bravo AF: 0.519

Asia WGS AF: 0.367 AC: 1272 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.78

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: rs9465982; hg19: chr6-21178282;