6-20637075-T-C

Variant names:

• chr6-20637075-T-C
• rs9368215
• NM_017774.3:c.287-12218T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.287-12218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 150,446 control chromosomes in the GnomAD database, including 31,438 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 0.64 (31438 hom., cov: 28)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.287-12218T>C		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.287-12218T>C		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.287-12218T>C		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.287-12218T>C		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 96816 AN: 150346 Hom.: 31437 Cov.: 28

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.644 AC: 96856 AN: 150446 Hom.: 31438 Cov.: 28 AF XY: 0.647 AC XY: 47389 AN XY: 73286

African (AFR) AF: 0.590 AC: 24106 AN: 40846

American (AMR) AF: 0.674 AC: 10211 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3468

East Asian (EAS) AF: 0.818 AC: 4145 AN: 5066

South Asian (SAS) AF: 0.725 AC: 3465 AN: 4780

European-Finnish (FIN) AF: 0.664 AC: 6626 AN: 9978

Middle Eastern (MID) AF: 0.738 AC: 214 AN: 290

European-Non Finnish (NFE) AF: 0.647 AC: 43913 AN: 67864

Other (OTH) AF: 0.663 AC: 1394 AN: 2102

Alfa AF: 0.654 Hom.: 54957

Bravo AF: 0.641

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.092
DANN	Benign	0.39
PhyloP100		-1.1
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: rs9368215; hg19: chr6-20637306;