rs9295496

chr6-21148833-A-G

Variant summary

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

The NM_017774.3(CDKAL1):c.1299+40370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,044 control chromosomes in the GnomAD database, including 11,303 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 0.38 (11303 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.1299+40370A>G		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+40370A>G		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.1299+40370A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57044 AN: 151926 Hom.: 11269 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.376 AC: 57130 AN: 152044 Hom.: 11303 Cov.: 32 AF XY: 0.373 AC XY: 27738 AN XY: 74328

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.353

Alfa AF: 0.339 Hom.: 11600

Bravo AF: 0.375

Asia WGS AF: 0.357 AC: 1240 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.36
Dann	Benign	0.73

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: rs9295496; hg19: chr6-21149064;