6-21182747-A-G

Variant names:

• chr6-21182747-A-G
• rs9295501
• NM_017774.3:c.1300-15274A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017774.3(CDKAL1):​c.1300-15274A>G variant causes a intron change. The variant allele was found at a frequency of 0.0334 in 152,332 control chromosomes in the GnomAD database, including 234 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 0.033 (234 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.1300-15274A>G		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1300-15274A>G		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.1300-15274A>G		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5092 AN: 152212 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.00687

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0334 AC: 5092 AN: 152332 Hom.: 234 Cov.: 32 AF XY: 0.0377 AC XY: 2811 AN XY: 74486

African (AFR) AF: 0.00683 AC: 284 AN: 41584

American (AMR) AF: 0.0237 AC: 362 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.162 AC: 838 AN: 5182

South Asian (SAS) AF: 0.182 AC: 876 AN: 4826

European-Finnish (FIN) AF: 0.0531 AC: 564 AN: 10620

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1899 AN: 68030

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0259 Hom.: 36

Bravo AF: 0.0260

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		3.7
Mutation Taster		=98/2	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: rs9295501; hg19: chr6-21182978;