rs9295496

Variant names:

• chr6-21148833-A-G
• rs9295496
• NM_017774.3:c.1299+40370A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1299+40370A>G		intron_variant	Intron 13 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+40370A>G		intron_variant	Intron 13 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1299+40370A>G		intron_variant	Intron 11 of 13	2		ENSP00000367873.1

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

African (AFR) AF: 0.508 AC: 21074 AN: 41450

American (AMR) AF: 0.276 AC: 4212 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1137 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1440 AN: 5182

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4818

European-Finnish (FIN) AF: 0.329 AC: 3472 AN: 10542

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22854 AN: 67982

Other (OTH) AF: 0.353 AC: 747 AN: 2114

Alfa AF: 0.343 Hom.: 14909

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
PhyloP100		-0.51
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: rs9295496; hg19: chr6-21149064;