rs10440833

Positions:

• chr6-20687890-T-A
• chr6-20687890-T-G

Variant summary

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

The NM_017774.3(CDKAL1):​c.371+38513T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,942 control chromosomes in the GnomAD database, including 5,305 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 0.26 (5305 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.371+38513T>A		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+38513T>A		intron_variant		1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.371+38513T>A		intron_variant		2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39401 AN: 151826 Hom.: 5301 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.259 AC: 39409 AN: 151942 Hom.: 5305 Cov.: 32 AF XY: 0.266 AC XY: 19728 AN XY: 74250

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.245

Alfa AF: 0.169 Hom.: 355

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.13

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: rs10440833; hg19: chr6-20688121;